113-627: CREB-TF (CREB, cAMP response element-binding protein ) is a cellular transcription factor . It binds to certain DNA sequences called cAMP response elements (CRE), thereby increasing or decreasing the transcription of the genes . CREB was first described in 1987 as a cAMP -responsive transcription factor regulating the somatostatin gene. Genes whose transcription is regulated by CREB include: c-fos , BDNF , tyrosine hydroxylase , numerous neuropeptides (such as somatostatin , enkephalin , VGF , corticotropin-releasing hormone ), and genes involved in
226-520: A body length of up to 28 cm (11 in) long, and a tail slightly shorter than that. It weighs between 140 and 500 g (4.9 and 17.6 oz). Thought to have originated in northern China and neighbouring areas, this rodent has now spread to all continents except Antarctica , and is the dominant rat in Europe and much of North America. With rare exceptions, the brown rat lives wherever humans live, particularly in urban areas. Selective breeding of
339-876: A complex, by promoting (as an activator ), or blocking (as a repressor ) the recruitment of RNA polymerase (the enzyme that performs the transcription of genetic information from DNA to RNA) to specific genes. A defining feature of TFs is that they contain at least one DNA-binding domain (DBD), which attaches to a specific sequence of DNA adjacent to the genes that they regulate. TFs are grouped into classes based on their DBDs. Other proteins such as coactivators , chromatin remodelers , histone acetyltransferases , histone deacetylases , kinases , and methylases are also essential to gene regulation, but lack DNA-binding domains, and therefore are not TFs. TFs are of interest in medicine because TF mutations can cause specific diseases, and medications can be potentially targeted toward them. Transcription factors are essential for
452-439: A coordinated fashion to direct cell division , cell growth , and cell death throughout life; cell migration and organization ( body plan ) during embryonic development; and intermittently in response to signals from outside the cell, such as a hormone . There are approximately 1600 TFs in the human genome . Transcription factors are members of the proteome as well as regulome . TFs work alone or with other proteins in
565-512: A different strength of interaction. For example, although the consensus binding site for the TATA-binding protein (TBP) is TATAAAA, the TBP transcription factor can also bind similar sequences such as TATATAT or TATATAA. Because transcription factors can bind a set of related sequences and these sequences tend to be short, potential transcription factor binding sites can occur by chance if
678-403: A distinct "chirping", has been likened to laughter , and is interpreted as an expectation of something rewarding. Like most rat vocalizations, the chirping is too high in pitch for humans to hear without special equipment. Bat detectors are often used by pet owners for this purpose. In research studies, the chirping is associated with positive emotional feelings, and social bonding occurs with
791-452: A gene on a chromosome into RNA, and then the RNA is translated into protein. Any of these steps can be regulated to affect the production (and thus activity) of a transcription factor. An implication of this is that transcription factors can regulate themselves. For example, in a negative feedback loop, the transcription factor acts as its own repressor: If the transcription factor protein binds
904-421: A host cell to promote pathogenesis. A well studied example of this are the transcription-activator like effectors ( TAL effectors ) secreted by Xanthomonas bacteria. When injected into plants, these proteins can enter the nucleus of the plant cell, bind plant promoter sequences, and activate transcription of plant genes that aid in bacterial infection. TAL effectors contain a central repeat region in which there
1017-773: A living cell. Additional recognition specificity, however, may be obtained through the use of more than one DNA-binding domain (for example tandem DBDs in the same transcription factor or through dimerization of two transcription factors) that bind to two or more adjacent sequences of DNA. Transcription factors are of clinical significance for at least two reasons: (1) mutations can be associated with specific diseases, and (2) they can be targets of medications. Due to their important roles in development, intercellular signaling, and cell cycle, some human diseases have been associated with mutations in transcription factors. Many transcription factors are either tumor suppressors or oncogenes , and, thus, mutations or aberrant regulation of them
1130-532: A magnesium ion that facilitates binding to DNA. The cAMP response element (CRE) is the response element for CREB which contains the highly conserved nucleotide sequence, 5'-TGACGTCA-3’. CRE sites are typically found upstream of genes, within the promoter or enhancer regions. There are approximately 750,000 palindromic and half-site CREs in the human genome. However, the majority of these sites remain unbound due to cytosine methylation , which physically obstructs protein binding. A generalized sequence of events
1243-417: A major role in determining sex in humans. Cells can communicate with each other by releasing molecules that produce signaling cascades within another receptive cell. If the signal requires upregulation or downregulation of genes in the recipient cell, often transcription factors will be downstream in the signaling cascade. Estrogen signaling is an example of a fairly short signaling cascade that involves
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#17327867476681356-853: A methylated CpG site, 175 transcription factors (34%) that had enhanced binding if their binding sequence had a methylated CpG site, and 25 transcription factors (5%) were either inhibited or had enhanced binding depending on where in the binding sequence the methylated CpG was located. TET enzymes do not specifically bind to methylcytosine except when recruited (see DNA demethylation ). Multiple transcription factors important in cell differentiation and lineage specification, including NANOG , SALL4 A, WT1 , EBF1 , PU.1 , and E2A , have been shown to recruit TET enzymes to specific genomic loci (primarily enhancers) to act on methylcytosine (mC) and convert it to hydroxymethylcytosine hmC (and in most cases marking them for subsequent complete demethylation to cytosine). TET-mediated conversion of mC to hmC appears to disrupt
1469-474: A serious threat to many of New Zealand's native wildlife . Rat eradication programmes within New Zealand have led to rat-free zones on offshore islands and even on fenced "ecological islands" on the mainland. Before an eradication effort was launched in 2001, the sub-Antarctic Campbell Island had the highest population density of brown rats in the world. Similar to other rodents , brown rats may carry
1582-452: A smaller number. Therefore, approximately 10% of genes in the genome code for transcription factors, which makes this family the single largest family of human proteins. Furthermore, genes are often flanked by several binding sites for distinct transcription factors, and efficient expression of each of these genes requires the cooperative action of several different transcription factors (see, for example, hepatocyte nuclear factors ). Hence,
1695-417: A space next to their closest friend, also explained in the name; allo-grooming, so-called to distinguish it from self-grooming; and nosing, where a rat gently pushes with its nose at another rat near the neck. Rats are known to burrow extensively, both in the wild and in captivity, if given access to a suitable substrate . Rats generally begin a new burrow adjacent to an object or structure, as this provides
1808-446: A sturdy "roof" for the section of the burrow nearest to the ground's surface. Burrows usually develop to eventually include multiple levels of tunnels, as well as a secondary entrance. Older male rats will generally not burrow, while young males and females will burrow vigorously. Burrows provide rats with shelter and food storage, as well as safe, thermo-regulated nest sites. Rats use their burrows to escape from perceived threats in
1921-399: A terrible scattering of light within its vision. Brown rats are dichromats which perceive colors rather like a human with red-green colorblindness , and their colour saturation may be quite faint. Their blue perception, however, also has UV receptors, allowing them to see ultraviolet lights that humans and some other species cannot. The brown rat is nocturnal and is a good swimmer, both on
2034-457: A visit to the vet. The noise is best described as either a quick clicking or 'burring' sound, varying from animal to animal. Vigorous bruxing can be accompanied by boggling, where the eyes of the rat rapidly bulge and retract due to movement of the lower jaw muscles behind the eye socket. In addition, they commonly squeak along a range of tones from high, abrupt pain squeaks to soft, persistent 'singing' sounds during confrontations. The brown rat
2147-419: Is chromatin immunoprecipitation (ChIP). This technique relies on chemical fixation of chromatin with formaldehyde , followed by co-precipitation of DNA and the transcription factor of interest using an antibody that specifically targets that protein. The DNA sequences can then be identified by microarray or high-throughput sequencing ( ChIP-seq ) to determine transcription factor binding sites. If no antibody
2260-473: Is 822 g (29 oz) and they can reach a maximum length of 48.5 cm (19 in). Brown rats have acute hearing , are sensitive to ultrasound , and possess a very highly developed olfactory sense . Their average heart rate is 300 to 400 beats per minute, with a respiratory rate of around 100 per minute. The vision of a pigmented rat is poor, around 20/600, while a non-pigmented (albino) with no melanin in its eyes has both around 20/1200 vision and
2373-401: Is a protein that controls the rate of transcription of genetic information from DNA to messenger RNA , by binding to a specific DNA sequence . The function of TFs is to regulate—turn on and off—genes in order to make sure that they are expressed in the desired cells at the right time and in the right amount throughout the life of the cell and the organism. Groups of TFs function in
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#17327867476682486-481: Is a major agricultural area, Alberta is far from any seaport and only a portion of its eastern boundary with Saskatchewan provides a favorable entry route for rats. Brown rats cannot survive in the wild boreal forest to the north, the Rocky Mountains to the west, nor can they safely cross the semiarid High Plains of Montana to the south. The first brown rat did not reach Alberta until 1950, and in 1951,
2599-450: Is a simple relationship between the identity of two critical residues in sequential repeats and sequential DNA bases in the TAL effector's target site. This property likely makes it easier for these proteins to evolve in order to better compete with the defense mechanisms of the host cell. It is common in biology for important processes to have multiple layers of regulation and control. This
2712-510: Is a true omnivore and consumes almost anything, but cereals form a substantial part of its diet. The most-liked foods of brown rats include scrambled eggs , raw carrots, and cooked corn kernels. The least-liked foods are raw beets, peaches and raw celery. Foraging behavior is often population-specific, and varies by environment and food source. Brown rats living near a hatchery in West Virginia catch fingerling fish. Some colonies along
2825-405: Is also implicated in major depressive disorder. CREB is also thought to be involved in the growth of some types of cancer. Entrainment of the mammalian circadian clock is established via light induction of PER . Light excites melanopsin -containing photosensitive retinal ganglion cells which signal to the suprachiasmatic nucleus (SCN) via the retinohypothalamic tract (RHT). Excitation of
2938-455: Is also true with transcription factors: Not only do transcription factors control the rates of transcription to regulate the amounts of gene products (RNA and protein) available to the cell but transcription factors themselves are regulated (often by other transcription factors). Below is a brief synopsis of some of the ways that the activity of transcription factors can be regulated: Transcription factors (like all proteins) are transcribed from
3051-479: Is an additional important part of rat socialization. Huddling, an extreme form of herding and like chattering or "bruxing" is often used to communicate that they are feeling threatened and not to come near. The common rat has been more successful at inhabiting and building communities on 6 continents and are the only species to have occupied more land than humans. During the wintry months, rats will huddle into piles – usually cheek-to-cheek – to control humidity and keep
3164-534: Is associated with cancer. Three groups of transcription factors are known to be important in human cancer: (1) the NF-kappaB and AP-1 families, (2) the STAT family and (3) the steroid receptors . Below are a few of the better-studied examples: Approximately 10% of currently prescribed drugs directly target the nuclear receptor class of transcription factors. Examples include tamoxifen and bicalutamide for
3277-595: Is available for the protein of interest, DamID may be a convenient alternative. As described in more detail below, transcription factors may be classified by their (1) mechanism of action, (2) regulatory function, or (3) sequence homology (and hence structural similarity) in their DNA-binding domains. They are also classified by 3D structure of their DBD and the way it contacts DNA. There are two mechanistic classes of transcription factors: Transcription factors have been classified according to their regulatory function: Transcription factors are often classified based on
3390-442: Is called its DNA-binding domain. Below is a partial list of some of the major families of DNA-binding domains/transcription factors: The DNA sequence that a transcription factor binds to is called a transcription factor-binding site or response element . Transcription factors interact with their binding sites using a combination of electrostatic (of which hydrogen bonds are a special case) and Van der Waals forces . Due to
3503-506: Is estimated that brown rat populations will see an increase. In tropical and desert regions, brown rat occurrence tends to be limited to human-modified habitats. Contiguous rat-free areas in the world include the continent of Antarctica, the Arctic , some isolated islands, the Canadian province of Alberta , and certain conservation areas in New Zealand. Most of Australia apart from
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3616-410: Is estimated, with predators and interspecies conflict as major causes. When lactating, female rats display a 24-hour rhythm of maternal behavior, and will usually spend more time attending to smaller litters than large ones. Brown rats live in large, hierarchical groups, either in burrows or subsurface places, such as sewers and cellars. When food is in short supply, the rats lower in social order are
3729-403: Is followed by guanine in the 5' to 3' DNA sequence, a CpG site .) Methylation of CpG sites in a promoter region of a gene usually represses gene transcription, while methylation of CpGs in the body of a gene increases expression. TET enzymes play a central role in demethylation of methylated cytosines. Demethylation of CpGs in a gene promoter by TET enzyme activity increases transcription of
3842-479: Is found and eliminated, the rats are unable to re-infest it from an adjacent one. Isolated islands are also able to eliminate rat populations because of low human population density and the geographic distance from other rat populations. Many parts of the world have been populated by rats secondarily, where rats are now important invasive species that compete with and threaten local fauna. For instance, Norway rats reached North America between 1750 and 1775 and even in
3955-535: Is lower. It is difficult to determine the extent of their home range because they do not utilize a whole area but rather use regular runways to get from one location to another. There is great debate over the size of the population of rats in New York City , with estimates from almost 100 million rats to as few as 250,000. Experts suggest that New York is a particularly attractive place for rats because of its aging infrastructure and high poverty rates. In 2023,
4068-426: Is mediated via its basic leucine zipper domain ( bZIP domain ) as depicted in the image. Evidence suggests the β-adrenoceptor (a G-protein coupled receptor ) stimulates CREB signalling. CREB has many functions in many different organs, and some of its functions have been studied in relation to the brain. CREB proteins in neurons are thought to be involved in the formation of long-term memories; this has been shown in
4181-527: Is much safer to use near humans and other large animals than arsenic. By 1960, the number of rat infestations in Alberta had dropped to below 200 per year. In 2002, the province finally recorded its first year with zero rat infestations, and from 2002 to 2007 there were only two infestations found. After an infestation of rats in the Medicine Hat landfill was found in 2012, the province's rat-free status
4294-409: Is not clear that they are "drugable" but progress has been made on Pax2 and the notch pathway. Gene duplications have played a crucial role in the evolution of species. This applies particularly to transcription factors. Once they occur as duplicates, accumulated mutations encoding for one copy can take place without negatively affecting the regulation of downstream targets. However, changes of
4407-411: Is only significant during the subjective night. Michael Greenberg first demonstrated the role of CREB in the mammalian circadian clock in 1993 through a series of experiments that correlated phase-specific light pulses with CREB phosphorylation. In vitro, light during the subjective night increased phosphorylation of CREB rather than CREB protein levels. In vivo, phase shift-inducing light pulses during
4520-414: Is organized with the help of histones into compact particles called nucleosomes , where sequences of about 147 DNA base pairs make ~1.65 turns around histone protein octamers. DNA within nucleosomes is inaccessible to many transcription factors. Some transcription factors, so-called pioneer factors are still able to bind their DNA binding sites on the nucleosomal DNA. For most other transcription factors,
4633-482: Is punishable by a penalty of up to C$ 5,000 or up to 60 days in jail. The adjacent and similarly landlocked province of Saskatchewan initiated a rat control program in 1972, and has managed to reduce the number of rats in the province substantially, although they have not been eliminated. The Saskatchewan rat control program has considerably reduced the number of rats trying to enter Alberta. First arriving before 1800 (perhaps on James Cook's vessels), brown rats pose
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4746-652: Is restricted, she can extend pregnancy by over two weeks, and give birth to litters of normal number and weight. Males can ejaculate multiple times in a row, and this increases the likelihood of pregnancy as well as decreases the number of stillborns. Multiple ejaculation also means that males can mate with multiple females, and they exhibit more ejaculatory series when there are several oestrous females present. Males also copulate at shorter intervals than females. In group mating, females often switch partners. Dominant males have higher mating success and also provide females with more ejaculate, and females are more likely to use
4859-514: Is summarized as follows: A signal arrives at the cell surface, activates the corresponding receptor, which leads to the production of a second messenger such as cAMP or Ca , which in turn activates a protein kinase . This protein kinase translocates to the cell nucleus , where it activates a CREB protein. The activated CREB protein then binds to a CRE region, and is then bound to by CBP (CREB-binding protein), which coactivates it, allowing it to switch certain genes on or off. The DNA binding of CREB
4972-419: Is the largest rat-free populated area in the world. Rat invasions of Alberta were stopped and rats were eliminated by very aggressive government rat control measures, starting during the 1950s. The only Rattus species that is capable of surviving the climate of Alberta is the brown rat, which can only survive in the prairie region of the province, and even then must overwinter in buildings. Although it
5085-421: Is usually brown or dark grey, while the underparts are lighter grey or brown. The brown rat is a rather large murid and can weigh twice as much as a black rat ( Rattus rattus ) and many times more than a house mouse ( Mus musculus ). The head and body length ranges from 15 to 28 cm (5.9 to 11.0 in) while the tail ranges in length from 10.5 to 24 cm (4.1 to 9.4 in), therefore being shorter than
5198-514: The TET1 protein that initiates a pathway of DNA demethylation . EGR1, together with TET1, is employed in programming the distribution of methylation sites on brain DNA during brain development and in learning (see Epigenetics in learning and memory ). Transcription factors are modular in structure and contain the following domains : The portion ( domain ) of the transcription factor that binds DNA
5311-598: The black rat , his mention of a large percentage of albino specimens—not uncommon among wild populations of brown rats—adds credibility to this conclusion. Reliable reports dating to the 18th century document the presence of the brown rat in Ireland in 1722, England in 1730, France in 1735, Germany in 1750, and Spain in 1800, becoming widespread during the Industrial Revolution . It did not reach North America until around 1750–1755. As it spread from Asia,
5424-526: The dentate gyrus behaved similarly to rats treated with antidepressants. From post-mortem examinations it has also been shown that the cortices of patients with untreated major depressive disorder contain reduced concentrations of CREB compared to both healthy controls and patients treated with antidepressants. The function of CREB can be modulated via a signalling pathway resulting from the binding of serotonin and noradrenaline to post-synaptic G-protein coupled receptors. Dysfunction of these neurotransmitters
5537-920: The estrogen receptor transcription factor: Estrogen is secreted by tissues such as the ovaries and placenta , crosses the cell membrane of the recipient cell, and is bound by the estrogen receptor in the cell's cytoplasm . The estrogen receptor then goes to the cell's nucleus and binds to its DNA-binding sites , changing the transcriptional regulation of the associated genes. Not only do transcription factors act downstream of signaling cascades related to biological stimuli but they can also be downstream of signaling cascades involved in environmental stimuli. Examples include heat shock factor (HSF), which upregulates genes necessary for survival at higher temperatures, hypoxia inducible factor (HIF), which upregulates genes necessary for cell survival in low-oxygen environments, and sterol regulatory element binding protein (SREBP), which helps maintain proper lipid levels in
5650-566: The genomic level, DNA- sequencing and database research are commonly used. The protein version of the transcription factor is detectable by using specific antibodies . The sample is detected on a western blot . By using electrophoretic mobility shift assay (EMSA), the activation profile of transcription factors can be detected. A multiplex approach for activation profiling is a TF chip system where several different transcription factors can be detected in parallel. The most commonly used method for identifying transcription factor binding sites
5763-466: The misnomer . Berkenhout gave the brown rat the binomial name Rattus norvegicus , believing it had migrated to England from Norwegian ships in 1728. By the early to the middle part of the 19th century, British academics believed that the brown rat was not native to Norway, hypothesizing (incorrectly) that it may have come from Ireland, Gibraltar or across the English Channel with William
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#17327867476685876-427: The preinitiation complex and RNA polymerase . Thus, for a single transcription factor to initiate transcription, all of these other proteins must also be present, and the transcription factor must be in a state where it can bind to them if necessary. Cofactors are proteins that modulate the effects of transcription factors. Cofactors are interchangeable between specific gene promoters; the protein complex that occupies
5989-456: The sequence similarity and hence the tertiary structure of their DNA-binding domains. The following classification is based of the 3D structure of their DBD and the way it contacts DNA. It was first developed for Human TF and later extended to rodents and also to plants. There are numerous databases cataloging information about transcription factors, but their scope and utility vary dramatically. Some may contain only information about
6102-528: The Conqueror . As early as 1850, however, a new hypothesis of the rat's origins was beginning to develop. The British novelist Charles Dickens acknowledged this in his weekly journal, All the Year Round, writing: It is frequently called, in books and otherwise, the 'Norway rat', and it is said to have been imported into this country in a ship-load of timber from Norway. Against this hypothesis stands
6215-431: The DNA binding specificities of the single-copy Leafy transcription factor, which occurs in most land plants, have recently been elucidated. In that respect, a single-copy transcription factor can undergo a change of specificity through a promiscuous intermediate without losing function. Similar mechanisms have been proposed in the context of all alternative phylogenetic hypotheses, and the role of transcription factors in
6328-411: The DNA of its own gene, it down-regulates the production of more of itself. This is one mechanism to maintain low levels of a transcription factor in a cell. In eukaryotes , transcription factors (like most proteins) are transcribed in the nucleus but are then translated in the cell's cytoplasm . Many proteins that are active in the nucleus contain nuclear localization signals that direct them to
6441-430: The DNA sequence is long enough. It is unlikely, however, that a transcription factor will bind all compatible sequences in the genome of the cell . Other constraints, such as DNA accessibility in the cell or availability of cofactors may also help dictate where a transcription factor will actually bind. Thus, given the genome sequence, it is still difficult to predict where a transcription factor will actually bind in
6554-712: The Faroe Islands may be among the lowest recorded worldwide. Hawadax Island (formerly known as Rat Island) in Alaska is thought to have been the first island in the Aleutians to be invaded by Norway rats (the Brown rat) when a Japanese ship went aground in the 1780s. They had a devastating effect on the native bird life. An eradication program was started in 2007 and the island was declared rat-free in June 2009. Alberta
6667-505: The RHT signals the release of glutamate which is received by NMDA receptors on SCN, resulting in a calcium influx into the SCN. Calcium induces the activity of Ca/ calmodulin-dependent protein kinases , resulting in the activation of PKA , PKC , and CK2 . These kinases then phosphorylate CREB in a circadian manner that further regulates downstream gene expression. The phosphorylated CREB recognizes
6780-461: The Serine 133 residue. When activated, CREB protein recruits other transcriptional coactivators to bind to CRE promoter 5’ upstream region. Hydrophobic leucine amino acids are located along the inner edge of the alpha helix. These leucine residues tightly bind to leucine residues of another CREB protein forming a dimer. This chain of leucine residues forms the leucine zipper motif . The protein also has
6893-573: The United Kingdom, some figures show that the rat population has been rising, with estimations that 81 million rats reside in the UK Those figures would mean that there are 1.3 rats per person in the country. High rat populations in the UK are often attributed to the mild climate, which allow them higher survival rates during the winter. With the increase in global temperature and glacier retreat, it
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#17327867476687006-411: The actual proteins, some about their binding sites, or about their target genes. Examples include the following: Rattus norvegicus The brown rat ( Rattus norvegicus ), also known as the common rat , street rat , sewer rat , wharf rat , Hanover rat , Norway rat and Norwegian rat , is a widespread species of common rat . One of the largest muroids , it is a brown or grey rodent with
7119-467: The adjacent gene is either up- or down-regulated . Transcription factors use a variety of mechanisms for the regulation of gene expression. These mechanisms include: Transcription factors are one of the groups of proteins that read and interpret the genetic "blueprint" in the DNA. They bind to the DNA and help initiate a program of increased or decreased gene transcription. As such, they are vital for many important cellular processes. Below are some of
7232-432: The air warm as a heat-conserving function. Just like elderly rats are commonly groomed and nursed by their companions, nestling rats especially depend on heat from their mother, since they cannot regulate their own temperature. Other forms of interaction include: crawling under, which is literally the act of crawling underneath one another (this is common when the rat is feeling ill and helps them breathe); walking over to find
7345-521: The already established population in Suðuroy, or they were brought to the Faroe Islands with other ships is unknown. The Northern islands were invaded by the brown rat more than 100 years later, after Norwegians built and operated a whaling station in the village of Hvannasund on Borðoy from 1898 to 1920. From there, the brown rat spread to the neighbouring islands of Viðoy and Kunoy . A recent genomic analysis reveals three independent introductions of
7458-681: The banks of the Po River in Italy dive for mollusks , a practice demonstrating social learning among members of this species. Rats on the island of Norderoog in the North Sea stalk and kill sparrows and ducks. Also preyed upon by brown rats are chicks, mice and small lizards. Examination of a wild brown rat stomachs in Germany revealed 4,000 food items, most of which were plants, although studies have shown that brown rats prefer meat when given
7571-411: The binding of 5mC-binding proteins including MECP2 and MBD ( Methyl-CpG-binding domain ) proteins, facilitating nucleosome remodeling and the binding of transcription factors, thereby activating transcription of those genes. EGR1 is an important transcription factor in memory formation. It has an essential role in brain neuron epigenetic reprogramming. The transcription factor EGR1 recruits
7684-518: The brain can contribute to the development and progression of Huntington's disease . Abnormalities of a protein that interacts with the KID domain of CREB, the CREB-binding protein , (CBP) is associated with Rubinstein–Taybi syndrome . There is some evidence to suggest that the under-functioning of CREB is associated with major depressive disorder . Depressed rats with an overexpression of CREB in
7797-467: The brown rat generally displaced the black rat in areas where humans lived. In addition to being larger and more aggressive, the change from wooden structures and thatched roofs to bricked and tiled buildings favored the burrowing brown rats over the arboreal black rats. In addition, brown rats eat a wider variety of foods, and are more resistant to weather extremes. In the absence of humans, brown rats prefer damp environments, such as river banks. However,
7910-464: The brown rat has produced the fancy rat (rats kept as pets), as well as the laboratory rat (rats used as model organisms in biological research). Both fancy rats and laboratory rats are of the domesticated subspecies Rattus norvegicus domestica . Studies of wild rats in New York City have shown that populations living in different neighborhoods can evolve distinct genomic profiles over time, by slowly accruing different traits. The brown rat
8023-618: The brown rat spread to other parts of the world sometime in the Middle Ages. The question of when brown rats became commensal with humans remains unsettled, but as a species, they have spread and established themselves along routes of human migration and now live almost everywhere humans are. The brown rat may have been present in Europe as early as 1553, a conclusion drawn from an illustration and description by Swiss naturalist Conrad Gesner in his book Historiae animalium , published 1551–1558. Though Gesner's description could apply to
8136-411: The cAMP Response Element and serves as a transcription factor for Per1 and Per2 , two genes that regulate the mammalian circadian clock. This induction of PER protein can entrain the circadian clock to light/dark cycles inhibits its own transcription via a transcription-translation feedback loop which can advance or delay the circadian clock. However, the responsiveness of PER1 and PER2 protein induction
8249-450: The cell. Many transcription factors, especially some that are proto-oncogenes or tumor suppressors , help regulate the cell cycle and as such determine how large a cell will get and when it can divide into two daughter cells. One example is the Myc oncogene, which has important roles in cell growth and apoptosis . Transcription factors can also be used to alter gene expression in
8362-427: The city appointed Kathleen Corradi as the first Rat Czar , a position created to address the city's rat population. The position focuses on instituting policies measures to curb the population such as garbage regulation and additional rat trapping . In addition to sewers, rats are very comfortable living in alleyways and residential buildings, as there is usually a large and continuous food source in those areas. In
8475-408: The combinatorial use of a subset of the approximately 2000 human transcription factors easily accounts for the unique regulation of each gene in the human genome during development . Transcription factors bind to either enhancer or promoter regions of DNA adjacent to the genes that they regulate based on recognizing specific DNA motifs. Depending on the transcription factor, the transcription of
8588-476: The costs to the landowner or municipality. In the first year of the rat control program, 64 t (71 short tons) of arsenic trioxide were spread throughout 8,000 buildings on farms along the Saskatchewan border. However, in 1953 the much safer and more effective rodenticide warfarin was introduced to replace arsenic. Warfarin is an anticoagulant that was approved as a drug for human use in 1954 and
8701-587: The early 20th century, from 1925 to 1927, 50% of ships entering the port of New York were rat infested. The brown rat was first observed on the Faroe Islands in 1768. It is thought that the first individuals arrived on the southernmost island, Suðuroy , via the wreck of a Norwegian ship that had stranded on the Scottish Isle of Lewis on its way from Trondheim to Dublin . The drifting wreck, carrying brown rats, drifted northwards until it reached
8814-426: The eastern and south-eastern coastal areas does not have reports of substantial rat occurrences. Antarctica is uninhabitable by rats. The Arctic has extremely cold winters that rats cannot survive outdoors, and the human population density is extremely low, making it difficult for rats to travel from one habitation to another, although they have arrived in many coastal areas by ship. When the occasional rat infestation
8927-653: The evolution of all species. The transcription factors have a role in resistance activity which is important for successful biocontrol activity. The resistant to oxidative stress and alkaline pH sensing were contributed from the transcription factor Yap1 and Rim101 of the Papiliotrema terrestris LS28 as molecular tools revealed an understanding of the genetic mechanisms underlying the biocontrol activity which supports disease management programs based on biological and integrated control. There are different technologies available to analyze transcription factors. On
9040-557: The fact that when the brown rat had become common in this country, it was unknown in Norway, although there was a small animal like a rat, but really a lemming , which made its home there. Academics began to prefer this etymology of the brown rat towards the end of the 19th century, as seen in the 1895 text Natural History by American scholar Alfred Henry Miles : The brown rat is the species common in England, and best known throughout
9153-462: The first to die. If a large fraction of a rat population is exterminated, the remaining rats will increase their reproductive rate, and quickly restore the old population level. The female is capable of becoming pregnant immediately after giving birth, and can nurse one litter while pregnant with another. She is able to produce and raise two healthy litters of normal size and weight without significantly changing her own food intake. However, when food
9266-475: The formation of spatial memory . CREB downregulation is implicated in the pathology of Alzheimer's disease and increasing the expression of CREB is being considered as a possible therapeutic target for Alzheimer's disease. CREB also has a role in photoentrainment in mammals. The following genes encode CREB or CREB-like proteins: CREB proteins are activated by phosphorylation from various kinases, including PKA , and Ca/calmodulin-dependent protein kinases on
9379-535: The gene that they regulate. Other transcription factors differentially regulate the expression of various genes by binding to enhancer regions of DNA adjacent to regulated genes. These transcription factors are critical to making sure that genes are expressed in the right cell at the right time and in the right amount, depending on the changing requirements of the organism. Many transcription factors in multicellular organisms are involved in development. Responding to stimuli, these transcription factors turn on/off
9492-469: The gene. The DNA binding sites of 519 transcription factors were evaluated. Of these, 169 transcription factors (33%) did not have CpG dinucleotides in their binding sites, and 33 transcription factors (6%) could bind to a CpG-containing motif but did not display a preference for a binding site with either a methylated or unmethylated CpG. There were 117 transcription factors (23%) that were inhibited from binding to their binding sequence if it contained
9605-451: The great majority are now linked to man-made environments, such as sewage systems. It is often said that there are as many rats in cities as people, but this varies from area to area depending on climate, living conditions, etc. Brown rats in cities tend not to wander extensively, often staying within 20 m (66 ft) of their nest if a suitable concentrated food supply is available, but they will range more widely where food availability
9718-494: The head and body. Adult weight ranges from 140 to 500 g (4.9 to 17.6 oz). Large individuals can reach 800 g (28 oz) but are not expected outside of domestic specimens. Stories of rats attaining sizes as big as cats are exaggerations, or misidentifications of larger rodents, such as the coypu and muskrat . It is common for breeding wild brown rats to weigh (sometimes considerably) less than 300 g (11 oz). The heaviest live Rattus norvegicus on record
9831-594: The important functions and biological roles transcription factors are involved in: In eukaryotes , an important class of transcription factors called general transcription factors (GTFs) are necessary for transcription to occur. Many of these GTFs do not actually bind DNA, but rather are part of the large transcription preinitiation complex that interacts with RNA polymerase directly. The most common GTFs are TFIIA , TFIIB , TFIID (see also TATA binding protein ), TFIIE , TFIIF , and TFIIH . The preinitiation complex binds to promoter regions of DNA upstream to
9944-416: The inactive form of CREB lose their ability to retain long-term memory. CREB is also important for the survival of neurons, as shown in genetically engineered mice, where CREB and CREM were deleted in the brain. If CREB is lost in the whole developing mouse embryo, the mice die immediately after birth, again highlighting the critical role of CREB in promoting neuronal survival. Disturbance of CREB function in
10057-503: The invasive brown rat to the Faroe Islands. Today the brown rat is found on seven of the eighteen Faroese islands, and is common in and around human habitations as well as in the wild. Although the brown rat is now common on all of the largest Faroese islands, only sparse information on the population is available in the literature. An investigation for infection with the spirochaete Leptospira interrogans did not find any infected animals, suggesting that Leptospira prevalence rates on
10170-410: The mammalian circadian clock ( PER1 , PER2 ). CREB is closely related in structure and function to CREM ( cAMP response element modulator ) and ATF-1 ( activating transcription factor-1 ) proteins. CREB proteins are expressed in many animals, including humans. CREB has a well-documented role in neuronal plasticity and long-term memory formation in the brain and has been shown to be integral in
10283-479: The marine snail Aplysia , the fruit fly Drosophila melanogaster , in rats and in mice (see CREB in Molecular and Cellular Cognition ). CREB is necessary for the late stage of long-term potentiation . CREB also has an important role in the development of drug addiction and even more so in psychological dependence . There are activator and repressor forms of CREB. Flies genetically engineered to overexpress
10396-432: The nature of these chemical interactions, most transcription factors bind DNA in a sequence specific manner. However, not all bases in the transcription factor-binding site may actually interact with the transcription factor. In addition, some of these interactions may be weaker than others. Thus, transcription factors do not bind just one sequence but are capable of binding a subset of closely related sequences, each with
10509-656: The nest. Although pups produce ultrasounds around any other rats at the age of 7 days, by 14 days old they significantly reduce ultrasound production around male rats as a defensive response. Adult rats will emit ultrasonic vocalizations in response to predators or perceived danger; the frequency and duration of such cries depends on the sex and reproductive status of the rat. The female rat also emit ultrasonic vocalizations during mating. Rats may also emit short, high frequency, ultrasonic, socially induced vocalization during rough and tumble play, before receiving morphine , or mating, and when tickled. The vocalization, described as
10622-530: The nucleosome should be actively unwound by molecular motors such as chromatin remodelers . Alternatively, the nucleosome can be partially unwrapped by thermal fluctuations, allowing temporary access to the transcription factor binding site. In many cases, a transcription factor needs to compete for binding to its DNA binding site with other transcription factors and histones or non-histone chromatin proteins. Pairs of transcription factors and other proteins can play antagonistic roles (activator versus repressor) in
10735-415: The nucleus. But, for many transcription factors, this is a key point in their regulation. Important classes of transcription factors such as some nuclear receptors must first bind a ligand while in the cytoplasm before they can relocate to the nucleus. Transcription factors may be activated (or deactivated) through their signal-sensing domain by a number of mechanisms including: In eukaryotes, DNA
10848-446: The option. In metropolitan areas, they survive mainly on discarded human food and anything else that can be eaten without negative consequences. The brown rat can breed throughout the year if conditions are suitable, with a female producing up to five litters a year. The gestation period is only 21 days, and litters can number up to 14, although seven is common. They reach sexual maturity in about five weeks. Under ideal conditions (for
10961-726: The others' back ends. If living space becomes limited, rats may turn to aggressive behavior, which may result in the death of some animals, reducing the burden over the living space. Rats, like most mammals, also form family groups of a mother and her young. This applies to both groups of males and females. However, rats are territorial animals, meaning that they usually act aggressively towards or scared of strange rats. Rats will fluff up their hair, hiss, squeal, and move their tails around when defending their territory. Rats will chase each other, groom each other, sleep in group nests, wrestle with each other, have dominance squabbles, communicate, and play in various other ways with each other. Huddling
11074-503: The promoter DNA and the amino acid sequence of the cofactor determine its spatial conformation. For example, certain steroid receptors can exchange cofactors with NF-κB , which is a switch between inflammation and cellular differentiation; thereby steroids can affect the inflammatory response and function of certain tissues. Transcription factors and methylated cytosines in DNA both have major roles in regulating gene expression. (Methylation of cytosine in DNA primarily occurs where cytosine
11187-399: The province launched a rat-control program that included shooting, poisoning, and gassing rats, and bulldozing or burning down some rat-infested buildings. The effort was backed by legislation that required every person and every municipality to destroy and prevent the establishment of designated pests. If they failed, the provincial government could carry out the necessary measures and charge
11300-430: The rat), this means that the population of females could increase by a factor of three and a half (half a litter of 7) in 8 weeks (5 weeks for sexual maturity and 3 weeks of gestation), corresponding to a population growing by a factor of 10 in just 15 weeks. As a result, the population can grow from 2 to 15,000 in a year. The maximum life span is three years, although most barely manage one. A yearly mortality rate of 95%
11413-515: The regulation of gene expression and are, as a consequence, found in all living organisms. The number of transcription factors found within an organism increases with genome size, and larger genomes tend to have more transcription factors per gene. There are approximately 2800 proteins in the human genome that contain DNA-binding domains, and 1600 of these are presumed to function as transcription factors, though other studies indicate it to be
11526-425: The regulation of the same gene . Most transcription factors do not work alone. Many large TF families form complex homotypic or heterotypic interactions through dimerization. For gene transcription to occur, a number of transcription factors must bind to DNA regulatory sequences. This collection of transcription factors, in turn, recruit intermediary proteins such as cofactors that allow efficient recruitment of
11639-981: The sperm of dominant males for fertilization. In mating, female rats show a clear mating preference for unknown males versus males that they have already mated with (also known as the Coolidge effect ), and will often resume copulatory behavior when introduced to a novel sexual partner. Females also prefer to mate with males who have not experienced social stress during adolescence, and can determine which males were stressed even without any observed difference in sexual performance of males experiencing stress during adolescence and not. Rats commonly groom each other and sleep together. Rats are said to establish an order of hierarchy, so one rat will be dominant over another one. Groups of rats tend to "play fight", which can involve any combination of jumping, chasing, tumbling, and "boxing". Play fighting involves rats going for each other's necks, while serious fighting involves strikes at
11752-521: The subjective night correlated with CREB phosphorylation in the SCN. Experiments by Gunther Schutz in 2002 demonstrated that mutant mice lacking the Ser142 phosphorylation site failed to induce the clock regulatory gene mPer1 in response to a light pulse. Furthermore, these mutant mice had difficulty entraining to light-dark cycles. Transcription factor In molecular biology , a transcription factor ( TF ) (or sequence-specific DNA-binding factor )
11865-656: The surface and underwater, and has been observed climbing slim round metal poles several feet in order to reach garden bird feeders. Brown rats dig well, and often excavate extensive burrow systems. A 2007 study found brown rats to possess metacognition , a mental ability previously only found in humans and some other primates, but further analysis suggested they may have been following simple operant conditioning principles. Brown rats are capable of producing ultrasonic vocalizations. As pups, young rats use different types of ultrasonic cries to elicit and direct maternal search behavior, as well as to regulate their mother's movements in
11978-406: The surrounding environment; for example, rats will retreat to their burrows following a sudden, loud noise or while fleeing an intruder. Burrowing can therefore be described as a "pre-encounter defensive behavior", as opposed to a "post-encounter defensive behavior", such as flight, freezing, or avoidance of a threatening stimulus. Possibly originating from the plains of northern China and Mongolia,
12091-412: The tickler, resulting in the rats becoming conditioned to seek the tickling. However, as the rats age, the tendency to chirp appears to decline. Brown rats also produce communicative noises capable of being heard by humans. The most commonly heard in domestic rats is bruxing, or teeth-grinding, which is most usually triggered by happiness, but can also be 'self-comforting' in stressful situations, such as
12204-447: The transcription of the appropriate genes, which, in turn, allows for changes in cell morphology or activities needed for cell fate determination and cellular differentiation . The Hox transcription factor family, for example, is important for proper body pattern formation in organisms as diverse as fruit flies to humans. Another example is the transcription factor encoded by the sex-determining region Y (SRY) gene, which plays
12317-495: The treatment of breast and prostate cancer , respectively, and various types of anti-inflammatory and anabolic steroids . In addition, transcription factors are often indirectly modulated by drugs through signaling cascades . It might be possible to directly target other less-explored transcription factors such as NF-κB with drugs. Transcription factors outside the nuclear receptor family are thought to be more difficult to target with small molecule therapeutics since it
12430-472: The village of Hvalba . Dispersion afterwards appears to have been fast, including all of Suðuroy within a year. In 1769, they were observed in Tórshavn on the southern part of Streymoy , and a decade later, in the villages in the northern part of this island. From here, they crossed the strait and occupied Eysturoy during the years 1776 to 1779. In 1779, they reached Vagar . Whether the rats dispersed from
12543-445: The world. It is said to have travelled from Persia to England less than two hundred years ago and to have spread from thence to other countries visited by English ships. Though the assumptions surrounding this species' origins were not yet the same as modern ones, by the 20th century, it was believed among naturalists that the brown rat did not originate in Norway, rather the species came from central Asia and (likely) China. The fur
12656-599: Was originally called the "Hanover rat" by people wishing to link problems in 18th-century England with the House of Hanover . It is not known for certain why the brown rat is named Rattus norvegicus (Norwegian rat), as it did not originate from Norway. However, the English naturalist John Berkenhout , author of the 1769 book Outlines of the Natural History of Great Britain , is most likely responsible for popularizing
12769-690: Was questioned, but provincial government rat control specialists brought in excavating machinery, dug out, shot, and poisoned 147 rats in the landfill, and no live rats were found thereafter. In 2013, the number of rat infestations in Alberta dropped to zero again. Alberta defines an infestation as two or more rats found at the same location, since a single rat cannot reproduce. About a dozen single rats enter Alberta in an average year and are killed by provincial rat control specialists before they can reproduce. Only zoos, universities, and research institutes are allowed to keep caged rats in Alberta, and possession of unlicensed rats, including fancy rats by anyone else
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