97-418: Histone H1 is one of the five main histone protein families which are components of chromatin in eukaryotic cells. Though highly conserved , it is nevertheless the most variable histone in sequence across species. Metazoan H1 proteins feature a central globular "winged helix" domain and long C- and short N-terminal tails. H1 is involved with the packing of the "beads on a string" sub-structures into
194-555: A blood bank for blood transfusion . The vast majority of vertebrates, including mammals and humans, have red blood cells. Red blood cells are cells present in blood to transport oxygen. The only known vertebrates without red blood cells are the crocodile icefish (family Channichthyidae ); they live in very oxygen-rich cold water and transport oxygen freely dissolved in their blood. While they no longer use hemoglobin, remnants of hemoglobin genes can be found in their genome . Vertebrate red blood cells consist mainly of hemoglobin ,
291-455: A cell nucleus . In comparison, the red blood cells of other vertebrates have nuclei; the only known exceptions are salamanders of the family Plethodontidae , where five different clades has evolved various degrees of enucleated red blood cells (most evolved in some species of the genus Batrachoseps ), and fish of the genus Maurolicus . The elimination of the nucleus in vertebrate red blood cells has been offered as an explanation for
388-691: A torus -shaped rim on the edge of the disk. This shape allows for a high surface-area-to-volume (SA/V) ratio to facilitate diffusion of gases. However, there are some exceptions concerning shape in the artiodactyl order (even-toed ungulates including cattle, deer, and their relatives), which displays a wide variety of bizarre red blood cell morphologies: small and highly ovaloid cells in llamas and camels (family Camelidae ), tiny spherical cells in mouse deer (family Tragulidae ), and cells which assume fusiform, lanceolate, crescentic, and irregularly polygonal and other angular forms in red deer and wapiti (family Cervidae ). Members of this order have clearly evolved
485-404: A ' helix turn helix turn helix' motif (DNA-binding protein motif that recognize specific DNA sequence). They also share the feature of long 'tails' on one end of the amino acid structure - this being the location of post-translational modification (see below). Archaeal histone only contains a H3-H4 like dimeric structure made out of a single type of unit. Such dimeric structures can stack into
582-420: A complex metalloprotein containing heme groups whose iron atoms temporarily bind to oxygen molecules (O 2 ) in the lungs or gills and release them throughout the body. Oxygen can easily diffuse through the red blood cell's cell membrane . Hemoglobin in the red blood cells also carries some of the waste product carbon dioxide back from the tissues; most waste carbon dioxide, however, is transported back to
679-470: A core promoter prevents the initiation of transcription in vitro, and Michael Grunstein demonstrated that histones repress transcription in vivo, leading to the idea of the nucleosome as a general gene repressor. Relief from repression is believed to involve both histone modification and the action of chromatin-remodeling complexes. Vincent Allfrey and Alfred Mirsky had earlier proposed a role of histone modification in transcriptional activation, regarded as
776-579: A few hundred up to a million copies per red blood cell. Approximately 25 of these membrane proteins carry the various blood group antigens, such as the A, B and Rh antigens, among many others. These membrane proteins can perform a wide diversity of functions, such as transporting ions and molecules across the red cell membrane, adhesion and interaction with other cells such as endothelial cells, as signaling receptors, as well as other currently unknown functions. The blood types of humans are due to variations in surface glycoproteins of red blood cells. Disorders of
873-482: A high order structure, whose details have not yet been solved. H1 found in protists and bacteria, otherwise known as nucleoproteins HC1 and HC2 ( Pfam PF07432 , PF07382 ), lack the central domain and the N-terminal tail. H1 is less conserved than core histones. The globular domain is the most conserved part of H1. Unlike the other histones, H1 does not make up the nucleosome "bead". Instead, it sits on top of
970-569: A higher number of histone variants providing a variety of different functions. Recent data are accumulating about the roles of diverse histone variants highlighting the functional links between variants and the delicate regulation of organism development. Histone variants proteins from different organisms, their classification and variant specific features can be found in "HistoneDB 2.0 - Variants" database. Several pseudogenes have also been discovered and identified in very close sequences of their respective functional ortholog genes. The following
1067-604: A key role in the CO 2 transport process, for two reasons. First, because, besides hemoglobin, they contain a large number of copies of the enzyme carbonic anhydrase on the inside of their cell membrane. Carbonic anhydrase, as its name suggests, acts as a catalyst of the exchange between carbonic acid and carbon dioxide (which is the anhydride of carbonic acid). Because it is a catalyst, it can affect many CO 2 molecules, so it performs its essential role without needing as many copies as are needed for O 2 transport by hemoglobin. In
SECTION 10
#17327833626061164-596: A left-handed super-helical turn to give a particle of around 100 Angstroms across. The linker histone H1 binds the nucleosome at the entry and exit sites of the DNA, thus locking the DNA into place and allowing the formation of higher order structure. The most basic such formation is the 10 nm fiber or beads on a string conformation. This involves the wrapping of DNA around nucleosomes with approximately 50 base pairs of DNA separating each pair of nucleosomes (also referred to as linker DNA ). Higher-order structures include
1261-660: A minimum thickness in the centre of 0.8–1 μm, being much smaller than most other human cells . These cells have an average volume of about 90 fL with a surface area of about 136 μm , and can swell up to a sphere shape containing 150 fL, without membrane distension. Adult humans have roughly 20–30 trillion red blood cells at any given time, constituting approximately 70% of all cells by number. Women have about 4–5 million red blood cells per microliter (cubic millimeter) of blood and men about 5–6 million; people living at high altitudes with low oxygen tension will have more. Red blood cells are thus much more common than
1358-795: A mode of red blood cell development substantially different from the mammalian norm. Overall, mammalian red blood cells are remarkably flexible and deformable so as to squeeze through tiny capillaries , as well as to maximize their apposing surface by assuming a cigar shape, where they efficiently release their oxygen load. Red blood cells in mammals are unique amongst vertebrates as they do not have nuclei when mature. They do have nuclei during early phases of erythropoiesis , but extrude them during development as they mature; this provides more space for hemoglobin. The red blood cells without nuclei, called reticulocytes , subsequently lose all other cellular organelles such as their mitochondria , Golgi apparatus and endoplasmic reticulum . The spleen acts as
1455-782: A molecular manifestation of epigenetics. Michael Grunstein and David Allis found support for this proposal, in the importance of histone acetylation for transcription in yeast and the activity of the transcriptional activator Gcn5 as a histone acetyltransferase. The discovery of the H5 histone appears to date back to the 1970s, and it is now considered an isoform of Histone H1 . Erythrocytes Red blood cells ( RBCs ), referred to as erythrocytes (from Ancient Greek erythros 'red' and kytos 'hollow vessel', with - cyte translated as 'cell' in modern usage) in academia and medical publishing, also known as red cells , erythroid cells , and rarely haematids , are
1552-471: A pH buffer. In summary, carbon dioxide produced by cellular respiration diffuses very rapidly to areas of lower concentration, specifically into nearby capillaries. When it diffuses into a RBC, CO 2 is rapidly converted by the carbonic anhydrase found on the inside of the RBC membrane into bicarbonate ion. The bicarbonate ions in turn leave the RBC in exchange for chloride ions from the plasma, facilitated by
1649-782: A post-translational modification, and binding domains such as BRCT have been characterised. Most well-studied histone modifications are involved in control of transcription. Two histone modifications are particularly associated with active transcription: Three histone modifications are particularly associated with repressed genes: Analysis of histone modifications in embryonic stem cells (and other stem cells) revealed many gene promoters carrying both H3K4Me3 and H3K27Me3 , in other words these promoters display both activating and repressing marks simultaneously. This peculiar combination of modifications marks genes that are poised for transcription; they are not required in stem cells, but are rapidly required after differentiation into some lineages. Once
1746-420: A reservoir of red blood cells, but this effect is somewhat limited in humans. In some other mammals such as dogs and horses, the spleen sequesters large numbers of red blood cells, which are dumped into the blood during times of exertion stress, yielding a higher oxygen transport capacity. A typical human red blood cell has a disk diameter of approximately 6.2–8.2 μm and a maximum thickness of 2–2.5 μm and
1843-463: A result of not containing mitochondria , red blood cells use none of the oxygen they transport; instead they produce the energy carrier ATP by the glycolysis of glucose and lactic acid fermentation on the resulting pyruvate . Furthermore, the pentose phosphate pathway plays an important role in red blood cells; see glucose-6-phosphate dehydrogenase deficiency for more information. As red blood cells contain no nucleus, protein biosynthesis
1940-421: A signalling gas that acts to relax vessel walls. It is believed that the cardioprotective effects of garlic are due to red blood cells converting its sulfur compounds into hydrogen sulfide. Red blood cells also play a part in the body's immune response : when lysed by pathogens such as bacteria, their hemoglobin releases free radicals , which break down the pathogen's cell wall and membrane, killing it. As
2037-411: A specific class of major histones but also have their own feature that is distinct from the major histones. These minor histones usually carry out specific functions of the chromatin metabolism. For example, histone H3-like CENPA is associated with only the centromere region of the chromosome. Histone H2A variant H2A.Z is associated with the promoters of actively transcribed genes and also involved in
SECTION 20
#17327833626062134-964: A tall superhelix ("hypernucleosome") onto which DNA coils in a manner similar to nucleosome spools. Only some archaeal histones have tails. The distance between the spools around which eukaryotic cells wind their DNA has been determined to range from 59 to 70 Å. In all, histones make five types of interactions with DNA: The highly basic nature of histones, aside from facilitating DNA-histone interactions, contributes to their water solubility. Histones are subject to post translational modification by enzymes primarily on their N-terminal tails, but also in their globular domains. Such modifications include methylation , citrullination , acetylation , phosphorylation , SUMOylation , ubiquitination , and ADP-ribosylation . This affects their function of gene regulation. In general, genes that are active have less bound histone, while inactive genes are highly associated with histones during interphase . It also appears that
2231-429: A third of the total cell volume. Hemoglobin is responsible for the transport of more than 98% of the oxygen in the body (the remaining oxygen is carried dissolved in the blood plasma ). The red blood cells of an average adult human male store collectively about 2.5 grams of iron, representing about 65% of the total iron contained in the body. Red blood cells in mammals are anucleate when mature, meaning that they lack
2328-412: A typical lipid bilayer , similar to what can be found in virtually all human cells. Simply put, this lipid bilayer is composed of cholesterol and phospholipids in equal proportions by weight. The lipid composition is important as it defines many physical properties such as membrane permeability and fluidity. Additionally, the activity of many membrane proteins is regulated by interactions with lipids in
2425-472: A very informative mark and dominates the known histone modification functions. Recently it has been shown, that the addition of a serotonin group to the position 5 glutamine of H3, happens in serotonergic cells such as neurons. This is part of the differentiation of the serotonergic cells. This post-translational modification happens in conjunction with the H3K4me3 modification. The serotonylation potentiates
2522-562: Is histone H5 , which is only found in avian erythrocytes , which are unlike mammalian erythrocytes in that they have nuclei . Another isoform is the oocyte/ zygotic H1M isoform (also known as B4 or H1foo), found in sea urchins, frogs, mice, and humans, which is replaced in the embryo by somatic isoforms H1A-E, and H10 which resembles H5. Despite having more negative charges than somatic isoforms, H1M binds with higher affinity to mitotic chromosomes in Xenopus egg extracts. Like other histones,
2619-485: Is a list of human histone proteins, genes and pseudogenes: The nucleosome core is formed of two H2A-H2B dimers and a H3-H4 tetramer, forming two nearly symmetrical halves by tertiary structure ( C2 symmetry; one macromolecule is the mirror image of the other). The H2A-H2B dimers and H3-H4 tetramer also show pseudodyad symmetry. The 4 'core' histones (H2A, H2B, H3 and H4) are relatively similar in structure and are highly conserved through evolution , all featuring
2716-630: Is a transcription factor which activates histone gene transcription on chromosomes 1 and 6 of human cells. NPAT is also a substrate of cyclin E-Cdk2, which is required for the transition between G1 phase and S phase. NPAT activates histone gene expression only after it has been phosphorylated by the G1/S-Cdk cyclin E-Cdk2 in early S phase. This shows an important regulatory link between cell-cycle control and histone synthesis. Histones were discovered in 1884 by Albrecht Kossel . The word "histone" dates from
2813-461: Is a very bright red in color. Flushed, confused patients with a saturation reading of 100% on pulse oximetry are sometimes found to be suffering from carbon monoxide poisoning. Having oxygen-carrying proteins inside specialized cells (as opposed to oxygen carriers being dissolved in body fluid) was an important step in the evolution of vertebrates as it allows for less viscous blood, higher concentrations of oxygen, and better diffusion of oxygen from
2910-743: Is chromatin bound. H1 compacts and stabilizes DNA under force and during chromatin assembly, which suggests that dynamic binding of H1 may provide protection for DNA in situations where nucleosomes need to be removed. Cytoplasmic factors appear to be necessary for the dynamic exchange of histone H1 on chromatin, but these have yet to be specifically identified. H1 dynamics may be mediated to some degree by O-glycosylation and phosphorylation. O-glycosylation of H1 may promote chromatin condensation and compaction. Phosphorylation during interphase has been shown to decrease H1 affinity for chromatin and may promote chromatin decondensation and active transcription. However, during mitosis phosphorylation has been shown to increase
3007-641: Is currently assumed to be absent in these cells. Because of the lack of nuclei and organelles, mature red blood cells do not contain DNA and cannot synthesize any RNA (although it does contain RNAs), and consequently cannot divide and have limited repair capabilities. The inability to carry out protein synthesis means that no virus can evolve to target mammalian red blood cells. However, infection with parvoviruses (such as human parvovirus B19 ) can affect erythroid precursors while they still have DNA, as recognized by
Histone H1 - Misplaced Pages Continue
3104-525: Is reduced to about 9 micrometers (0.09 mm) of 30 nm diameter chromatin fibers. There are five families of histones, which are designated H1/H5 (linker histones), H2, H3, and H4 (core histones). The nucleosome core is formed of two H2A-H2B dimers and a H3-H4 tetramer . The tight wrapping of DNA around histones, is to a large degree, a result of electrostatic attraction between the positively charged histones and negatively charged phosphate backbone of DNA. Histones may be chemically modified through
3201-407: Is responsible for the red color of the cells and the blood. Each human red blood cell contains approximately 270 million hemoglobin molecules. The cell membrane is composed of proteins and lipids , and this structure provides properties essential for physiological cell function such as deformability and stability of the blood cell while traversing the circulatory system and specifically
3298-499: Is the synthesis of histone proteins: H1, H2A, H2B, H3, H4. These proteins are synthesized during S phase of the cell cycle. There are different mechanisms which contribute to the increase of histone synthesis. Yeast carry one or two copies of each histone gene, which are not clustered but rather scattered throughout chromosomes. Histone gene transcription is controlled by multiple gene regulatory proteins such as transcription factors which bind to histone promoter regions. In budding yeast,
3395-401: Is this helical structure that allows for interaction between distinct dimers, particularly in a head-tail fashion (also called the handshake motif). The resulting four distinct dimers then come together to form one octameric nucleosome core, approximately 63 Angstroms in diameter (a solenoid (DNA) -like particle). Around 146 base pairs (bp) of DNA wrap around this core particle 1.65 times in
3492-493: Is uncertain whether H1 promotes a solenoid -like chromatin fiber, in which exposed linker DNA is shortened, or whether it merely promotes a change in the angle of adjacent nucleosomes, without affecting linker length However, linker histones have been demonstrated to drive the compaction of chromatin fibres that had been reconstituted in vitro using synthetic DNA arrays of the strong '601' nucleosome positioning element. Nuclease digestion and DNA footprinting experiments suggest that
3589-407: Is −15.7 milli volts (mV). Much of this potential appears to be contributed by the exposed sialic acid residues in the membrane: their removal results in zeta potential of −6.06 mV. Recall that respiration , as illustrated schematically here with a unit of carbohydrate, produces about as many molecules of carbon dioxide, CO 2 , as it consumes of oxygen, O 2 . Thus, the function of
3686-441: The band 3 anion transport protein colocated in the RBC membrane. The bicarbonate ion does not diffuse back out of the capillary, but is carried to the lung. In the lung the lower partial pressure of carbon dioxide in the alveoli causes carbon dioxide to diffuse rapidly from the capillary into the alveoli. The carbonic anhydrase in the red cells keeps the bicarbonate ion in equilibrium with carbon dioxide. So as carbon dioxide leaves
3783-440: The bone marrow and circulate for about 100–120 days in the body before their components are recycled by macrophages . Each circulation takes about 60 seconds (one minute). Approximately 84% of the cells in the human body are the 20–30 trillion red blood cells. Nearly half of the blood's volume ( 40% to 45% ) is red blood cells. Packed red blood cells are red blood cells that have been donated, processed, and stored in
3880-415: The capillary network. In humans, mature red blood cells are flexible biconcave disks . They lack a cell nucleus (which is expelled during development ) and organelles , to accommodate maximum space for hemoglobin; they can be viewed as sacks of hemoglobin, with a plasma membrane as the sack. Approximately 2.4 million new erythrocytes are produced per second in human adults. The cells develop in
3977-411: The pulmonary capillaries of the lungs as bicarbonate (HCO 3 ) dissolved in the blood plasma . Myoglobin , a compound related to hemoglobin, acts to store oxygen in muscle cells. The color of red blood cells is due to the heme group of hemoglobin. The blood plasma alone is straw-colored, but the red blood cells change color depending on the state of the hemoglobin: when combined with oxygen
Histone H1 - Misplaced Pages Continue
4074-763: The 3'hExo nuclease. SLBP levels are controlled by cell-cycle proteins, causing SLBP to accumulate as cells enter S phase and degrade as cells leave S phase. SLBP are marked for degradation by phosphorylation at two threonine residues by cyclin dependent kinases, possibly cyclin A/ cdk2, at the end of S phase. Metazoans also have multiple copies of histone genes clustered on chromosomes which are localized in structures called Cajal bodies as determined by genome-wide chromosome conformation capture analysis (4C-Seq). Nuclear protein Ataxia-Telangiectasia (NPAT), also known as nuclear protein coactivator of histone transcription,
4171-524: The 30 nm fiber (forming an irregular zigzag) and 100 nm fiber, these being the structures found in normal cells. During mitosis and meiosis, the condensed chromosomes are assembled through interactions between nucleosomes and other regulatory proteins. Histones are subdivided into canonical replication-dependent histones, whose genes are expressed during the S-phase of the cell cycle and replication-independent histone variants , expressed during
4268-501: The C-domain, and to the N-terminal substrate recognition domain of Clp/Hsp100 proteins. Despite the differences in their topology, these three folds share a homologous helix-strand-helix (HSH) motif. It's also proposed that they may have evolved from ribosomal proteins ( RPS6 / RPS15 ), both being short and basic proteins. Archaeal histones may well resemble the evolutionary precursors to eukaryotic histones. Histone proteins are among
4365-471: The DNA in the nucleus of higher organisms. Bonner and his postdoctoral fellow Ru Chih C. Huang showed that isolated chromatin would not support RNA transcription in the test tube, but if the histones were extracted from the chromatin, RNA could be transcribed from the remaining DNA. Their paper became a citation classic. Paul T'so and James Bonner had called together a World Congress on Histone Chemistry and Biology in 1964, in which it became clear that there
4462-433: The DNA, making it more accessible for gene expression. Five major families of histone proteins exist: H1/H5 , H2A , H2B , H3 , and H4 . Histones H2A, H2B, H3 and H4 are known as the core or nucleosomal histones, while histones H1/H5 are known as the linker histones. The core histones all exist as dimers , which are similar in that they all possess the histone fold domain: three alpha helices linked by two loops. It
4559-552: The FosB promoter in the nucleus accumbens of the brain, causing 61% increase in FosB expression. This would also increase expression of the splice variant Delta FosB . In the nucleus accumbens of the brain, Delta FosB functions as a "sustained molecular switch" and "master control protein" in the development of an addiction . About 7% of the US population is addicted to alcohol . In rats exposed to alcohol for up to 5 days, there
4656-437: The action of enzymes to regulate gene transcription. The most common modifications are the methylation of arginine or lysine residues or the acetylation of lysine. Methylation can affect how other proteins such as transcription factors interact with the nucleosomes. Lysine acetylation eliminates a positive charge on lysine thereby weakening the electrostatic attraction between histone and DNA, resulting in partial unwinding of
4753-506: The affinity of H1 for chromosomes and therefore promote mitotic chromosome condensation. The H1 family in animals includes multiple H1 isoforms that can be expressed in different or overlapping tissues and developmental stages within a single organism. The reason for these multiple isoforms remains unclear, but both their evolutionary conservation from sea urchin to humans as well as significant differences in their amino acid sequences suggest that they are not functionally equivalent. One isoform
4850-443: The bilayer. Unlike cholesterol, which is evenly distributed between the inner and outer leaflets, the 5 major phospholipids are asymmetrically disposed, as shown below: Outer monolayer Inner monolayer This asymmetric phospholipid distribution among the bilayer is the result of the function of several energy-dependent and energy-independent phospholipid transport proteins. Proteins called " Flippases " move phospholipids from
4947-528: The binding of the general transcription factor TFIID to the TATA box . What was said above of the chemistry of lysine methylation also applies to arginine methylation, and some protein domains—e.g., Tudor domains—can be specific for methyl arginine instead of methyl lysine. Arginine is known to be mono- or di-methylated, and methylation can be symmetric or asymmetric, potentially with different meanings. Enzymes called peptidylarginine deiminases (PADs) hydrolyze
SECTION 50
#17327833626065044-528: The biochemical characteristics of individual histones did not reveal how the histones interacted with each other or with DNA to which they were tightly bound. Also in the 1960s, Vincent Allfrey and Alfred Mirsky had suggested, based on their analyses of histones, that acetylation and methylation of histones could provide a transcriptional control mechanism, but did not have available the kind of detailed analysis that later investigators were able to conduct to show how such regulation could be gene-specific. Until
5141-433: The blood to the tissues. The size of red blood cells varies widely among vertebrate species; red blood cell width is on average about 25% larger than capillary diameter, and it has been hypothesized that this improves the oxygen transfer from red blood cells to tissues. The red blood cells of mammals are typically shaped as biconcave disks: flattened and depressed in the center, with a dumbbell -shaped cross section, and
5238-401: The body depleted of oxygen. Red blood cells can also synthesize nitric oxide enzymatically, using L-arginine as substrate, as do endothelial cells . Exposure of red blood cells to physiological levels of shear stress activates nitric oxide synthase and export of nitric oxide, which may contribute to the regulation of vascular tonus. Red blood cells can also produce hydrogen sulfide ,
5335-402: The brain are of central importance in addictions. Once particular epigenetic alterations occur, they appear to be long lasting "molecular scars" that may account for the persistence of addictions. Cigarette smokers (about 15% of the US population) are usually addicted to nicotine . After 7 days of nicotine treatment of mice, acetylation of both histone H3 and histone H4 was increased at
5432-482: The candidate gene for activation of histone gene expression is SBF. SBF is a transcription factor that is activated in late G1 phase, when it dissociates from its repressor Whi5 . This occurs when Whi5 is phosphorylated by Cdc8 which is a G1/S Cdk. Suppression of histone gene expression outside of S phases is dependent on Hir proteins which form inactive chromatin structure at the locus of histone genes, causing transcriptional activators to be blocked. In metazoans
5529-450: The capillary, act to reduce the oxygen binding affinity of hemoglobin, the Bohr effect . The second major contribution of RBC to carbon dioxide transport is that carbon dioxide directly reacts with globin protein components of hemoglobin to form carbaminohemoglobin compounds. As oxygen is released in the tissues, more CO 2 binds to hemoglobin, and as oxygen binds in the lung, it displaces
5626-510: The capillary, and CO 2 is displaced by O 2 on hemoglobin, sufficient bicarbonate ion converts rapidly to carbon dioxide to maintain the equilibrium. When red blood cells undergo shear stress in constricted vessels, they release ATP , which causes the vessel walls to relax and dilate so as to promote normal blood flow. When their hemoglobin molecules are deoxygenated, red blood cells release S-Nitrosothiols , which also act to dilate blood vessels, thus directing more blood to areas of
5723-424: The cell starts to differentiate, these bivalent promoters are resolved to either active or repressive states depending on the chosen lineage. Marking sites of DNA damage is an important function for histone modifications. Without a repair marker, DNA would get destroyed by damage accumulated from sources such as the ultraviolet radiation of the sun. Epigenetic modifications of histone tails in specific regions of
5820-509: The chemistry of the histone; methylation leaves the charge of the lysine intact and adds a minimal number of atoms so steric interactions are mostly unaffected. However, proteins containing Tudor, chromo or PHD domains, amongst others, can recognise lysine methylation with exquisite sensitivity and differentiate mono, di and tri-methyl lysine, to the extent that, for some lysines (e.g.: H4K20) mono, di and tri-methylation appear to have different meanings. Because of this, lysine methylation tends to be
5917-441: The circulatory system is as much about the transport of carbon dioxide as about the transport of oxygen. As stated elsewhere in this article, most of the carbon dioxide in the blood is in the form of bicarbonate ion. The bicarbonate provides a critical pH buffer . Thus, unlike hemoglobin for O 2 transport, there is a physiological advantage to not having a specific CO 2 transporter molecule. Red blood cells, nevertheless, play
SECTION 60
#17327833626066014-403: The early 1990s, histones were dismissed by most as inert packing material for eukaryotic nuclear DNA, a view based in part on the models of Mark Ptashne and others, who believed that transcription was activated by protein-DNA and protein-protein interactions on largely naked DNA templates, as is the case in bacteria. During the 1980s, Yahli Lorch and Roger Kornberg showed that a nucleosome on
6111-738: The gene. In Xenopus egg extracts, linker histone depletion causes ~2-fold lengthwise extension of mitotic chromosomes, while overexpression causes chromosomes to hypercompact into an inseparable mass. Complete knockout of H1 in vivo has not been achieved in multicellular organisms due to the existence of multiple isoforms that may be present in several gene clusters, but various linker histone isoforms have been depleted to varying degrees in Tetrahymena , C. elegans, Arabidopsis, fruit fly, and mouse, resulting in various organism-specific defects in nuclear morphology, chromatin structure, DNA methylation, and/or specific gene expression. While most histone H1 in
6208-470: The globular domain of histone H1 localizes near the nucleosome dyad, where it protects approximately 15-30 base pairs of additional DNA. In addition, experiments on reconstituted chromatin reveal a characteristic stem motif at the dyad in the presence of H1. Despite gaps in our understanding, a general model has emerged wherein H1's globular domain closes the nucleosome by crosslinking incoming and outgoing DNA, while
6305-487: The hemoglobin bound CO 2 , this is called the Haldane effect . Despite the fact that only a small amount of the CO 2 in blood is bound to hemoglobin in venous blood, a greater proportion of the change in CO 2 content between venous and arterial blood comes from the change in this bound CO 2 . That is, there is always an abundance of bicarbonate in blood, both venous and arterial, because of its aforementioned role as
6402-1090: The histone H1 family is extensively post-translationally modified (PTMs). This includes serine and threonine phosphorylation, lysine acetylation, lysine methylation and ubiquitination. These PTMs serve a variety of functions but are less well studied than the PTMs of other histones. Histone In biology , histones are highly basic proteins abundant in lysine and arginine residues that are found in eukaryotic cell nuclei and in most Archaeal phyla . They act as spools around which DNA winds to create structural units called nucleosomes . Nucleosomes in turn are wrapped into 30- nanometer fibers that form tightly packed chromatin . Histones prevent DNA from becoming tangled and protect it from DNA damage . In addition, histones play important roles in gene regulation and DNA replication . Without histones, unwound DNA in chromosomes would be very long. For example, each human cell has about 1.8 meters of DNA if completely stretched out; however, when wound about histones, this length
6499-420: The histones H2A and H2B can also be modified. Combinations of modifications, known as histone marks , are thought to constitute a code, the so-called " histone code ". Histone modifications act in diverse biological processes such as gene regulation , DNA repair , chromosome condensation ( mitosis ) and spermatogenesis ( meiosis ). The common nomenclature of histone modifications is: So H3K4me1 denotes
6596-436: The imine group of arginines and attach a keto group, so that there is one less positive charge on the amino acid residue. This process has been involved in the activation of gene expression by making the modified histones less tightly bound to DNA and thus making the chromatin more accessible. PADs can also produce the opposite effect by removing or inhibiting mono-methylation of arginine residues on histones and thus antagonizing
6693-499: The increase in the rate of histone synthesis is due to the increase in processing of pre-mRNA to its mature form as well as decrease in mRNA degradation; this results in an increase of active mRNA for translation of histone proteins. The mechanism for mRNA activation has been found to be the removal of a segment of the 3' end of the mRNA strand, and is dependent on association with stem-loop binding protein ( SLBP ). SLBP also stabilizes histone mRNAs during S phase by blocking degradation by
6790-537: The large genomes of eukaryotes inside cell nuclei: the compacted molecule is 40,000 times shorter than an unpacked molecule. Histones undergo posttranslational modifications that alter their interaction with DNA and nuclear proteins. The H3 and H4 histones have long tails protruding from the nucleosome , which can be covalently modified at several places. Modifications of the tail include methylation , acetylation , phosphorylation , ubiquitination , SUMOylation , citrullination , and ADP-ribosylation. The core of
6887-520: The late 19th century and is derived from the German word "Histon" , a word itself of uncertain origin, perhaps from Ancient Greek ἵστημι (hístēmi, “make stand”) or ἱστός (histós, “loom”). In the early 1960s, before the types of histones were known and before histones were known to be highly conserved across taxonomically diverse organisms, James F. Bonner and his collaborators began a study of these proteins that were known to be tightly associated with
6984-415: The lipid bilayer and membrane skeleton, likely enabling the red cell to maintain its favorable membrane surface area by preventing the membrane from collapsing (vesiculating). The zeta potential is an electrochemical property of cell surfaces that is determined by the net electrical charge of molecules exposed at the surface of cell membranes of the cell. The normal zeta potential of the red blood cell
7081-454: The lysine in position 4 of histone 3 located at the promoters of the c-fos and the C-C chemokine receptor 2 (ccr2) genes, activating those genes in the nucleus accumbens (NAc). c-fos is well known to be important in addiction . The ccr2 gene is also important in addiction, since mutational inactivation of this gene impairs addiction. The first step of chromatin structure duplication
7178-557: The membrane composition. The red blood cell membrane is composed of 3 layers: the glycocalyx on the exterior, which is rich in carbohydrates ; the lipid bilayer which contains many transmembrane proteins , besides its lipidic main constituents; and the membrane skeleton, a structural network of proteins located on the inner surface of the lipid bilayer. Half of the membrane mass in human and most mammalian red blood cells are proteins. The other half are lipids, namely phospholipids and cholesterol . The red blood cell membrane comprises
7275-432: The membrane skeleton are responsible for the deformability, flexibility and durability of the red blood cell, enabling it to squeeze through capillaries less than half the diameter of the red blood cell (7–8 μm) and recovering the discoid shape as soon as these cells stop receiving compressive forces, in a similar fashion to an object made of rubber. There are currently more than 50 known membrane proteins, which can exist in
7372-706: The monomethylation of the 4th residue (a lysine) from the start (i.e., the N-terminal ) of the H3 protein. A huge catalogue of histone modifications have been described, but a functional understanding of most is still lacking. Collectively, it is thought that histone modifications may underlie a histone code , whereby combinations of histone modifications have specific meanings. However, most functional data concerns individual prominent histone modifications that are biochemically amenable to detailed study. The addition of one, two, or many methyl groups to lysine has little effect on
7469-456: The most common type of blood cell and the vertebrate 's principal means of delivering oxygen ( O 2 ) to the body tissues —via blood flow through the circulatory system . Erythrocytes take up oxygen in the lungs , or in fish the gills , and release it into tissues while squeezing through the body's capillaries . The cytoplasm of a red blood cell is rich in hemoglobin (Hb), an iron -containing biomolecule that can bind oxygen and
7566-419: The most highly conserved proteins in eukaryotes, emphasizing their important role in the biology of the nucleus. In contrast mature sperm cells largely use protamines to package their genomic DNA, most likely because this allows them to achieve an even higher packaging ratio. There are some variant forms in some of the major classes. They share amino acid sequence homology and core structural similarity to
7663-441: The need to alter multiple lysines to have a significant effect on chromatin structure. The modification includes H3K27ac . Addition of a negatively charged phosphate group can lead to major changes in protein structure, leading to the well-characterised role of phosphorylation in controlling protein function. It is not clear what structural implications histone phosphorylation has, but histone phosphorylation has clear functions as
7760-430: The nucleus is bound to chromatin, H1 molecules shuttle between chromatin regions at a fairly high rate. It is difficult to understand how such a dynamic protein could be a structural component of chromatin, but it has been suggested that the steady-state equilibrium within the nucleus still strongly favors association between H1 and chromatin, meaning that despite its dynamics, the vast majority of H1 at any given timepoint
7857-458: The only eukaryotes that completely lack histones, but later studies showed that their DNA still encodes histone genes. Unlike the core histones, homologs of the lysine-rich linker histone (H1) proteins are found in bacteria, otherwise known as nucleoprotein HC1/HC2. It has been proposed that core histone proteins are evolutionarily related to the helical part of the extended AAA+ ATPase domain,
7954-403: The other blood particles: there are about 4,000–11,000 white blood cells and about 150,000–400,000 platelets per microliter. Human red blood cells take on average 60 seconds to complete one cycle of circulation. The blood's red color is due to the spectral properties of the hemic iron ions in hemoglobin . Each hemoglobin molecule carries four heme groups; hemoglobin constitutes about
8051-448: The outer to the inner monolayer, while others called " floppases " do the opposite operation, against a concentration gradient in an energy-dependent manner. Additionally, there are also " scramblase " proteins that move phospholipids in both directions at the same time, down their concentration gradients in an energy-independent manner. There is still considerable debate ongoing regarding the identity of these membrane maintenance proteins in
8148-598: The positive effect arginine methylation has on transcriptional activity. Addition of an acetyl group has a major chemical effect on lysine as it neutralises the positive charge. This reduces electrostatic attraction between the histone and the negatively charged DNA backbone, loosening the chromatin structure; highly acetylated histones form more accessible chromatin and tend to be associated with active transcription. Lysine acetylation appears to be less precise in meaning than methylation, in that histone acetyltransferases tend to act on more than one lysine; presumably this reflects
8245-445: The presence of giant pronormoblasts with viral particles and inclusion bodies , thus temporarily depleting the blood of reticulocytes and causing anemia . Human red blood cells are produced through a process named erythropoiesis , developing from committed stem cells to mature red blood cells in about 7 days. When matured, in a healthy individual these cells live in blood circulation for about 100 to 120 days (and 80 to 90 days in
8342-440: The presence of this catalyst carbon dioxide and carbonic acid reach an equilibrium very rapidly, while the red cells are still moving through the capillary. Thus it is the RBC that ensures that most of the CO 2 is transported as bicarbonate. At physiological pH the equilibrium strongly favors carbonic acid, which is mostly dissociated into bicarbonate ion. The H+ ions released by this rapid reaction within RBC, while still in
8439-430: The prevention of the spread of silent heterochromatin . Furthermore, H2A.Z has roles in chromatin for genome stability. Another H2A variant H2A.X is phosphorylated at S139 in regions around double-strand breaks and marks the region undergoing DNA repair . Histone H3.3 is associated with the body of actively transcribed genes. Histones act as spools around which DNA winds. This enables the compaction necessary to fit
8536-474: The proteins in these membranes are associated with many disorders, such as hereditary spherocytosis , hereditary elliptocytosis , hereditary stomatocytosis , and paroxysmal nocturnal hemoglobinuria . The red blood cell membrane proteins organized according to their function: Transport Cell adhesion Structural role – The following membrane proteins establish linkages with skeletal proteins and may play an important role in regulating cohesion between
8633-862: The red cell membrane. The maintenance of an asymmetric phospholipid distribution in the bilayer (such as an exclusive localization of PS and PIs in the inner monolayer) is critical for the cell integrity and function due to several reasons: The presence of specialized structures named " lipid rafts " in the red blood cell membrane have been described by recent studies. These are structures enriched in cholesterol and sphingolipids associated with specific membrane proteins, namely flotillins , STOMatins (band 7), G-proteins , and β-adrenergic receptors . Lipid rafts that have been implicated in cell signaling events in nonerythroid cells have been shown in erythroid cells to mediate β2-adregenic receptor signaling and increase cAMP levels, and thus regulating entry of malarial parasites into normal red cells. The proteins of
8730-468: The resulting oxyhemoglobin is scarlet, and when oxygen has been released the resulting deoxyhemoglobin is of a dark red burgundy color. However, blood can appear bluish when seen through the vessel wall and skin. Pulse oximetry takes advantage of the hemoglobin color change to directly measure the arterial blood oxygen saturation using colorimetric techniques. Hemoglobin also has a very high affinity for carbon monoxide , forming carboxyhemoglobin which
8827-424: The structure of histones has been evolutionarily conserved, as any deleterious mutations would be severely maladaptive. All histones have a highly positively charged N-terminus with many lysine and arginine residues. Core histones are found in the nuclei of eukaryotic cells and in most Archaeal phyla, but not in bacteria . The unicellular algae known as dinoflagellates were previously thought to be
8924-699: The structure, keeping in place the DNA that has wrapped around the nucleosome. H1 is present in half the amount of the other four histones, which contribute two molecules to each nucleosome bead. In addition to binding to the nucleosome, the H1 protein binds to the "linker DNA" (approximately 20-80 nucleotides in length) region between nucleosomes, helping stabilize the zig-zagged 30 nm chromatin fiber. Much has been learned about histone H1 from studies on purified chromatin fibers. Ionic extraction of linker histones from native or reconstituted chromatin promotes its unfolding under hypotonic conditions from fibers of 30 nm width to beads-on-a-string nucleosome arrays. It
9021-827: The subsequent accumulation of non-coding DNA in the genome . The argument runs as follows: Efficient gas transport requires red blood cells to pass through very narrow capillaries, and this constrains their size. In the absence of nuclear elimination, the accumulation of repeat sequences is constrained by the volume occupied by the nucleus, which increases with genome size. Nucleated red blood cells in mammals consist of two forms: normoblasts, which are normal erythropoietic precursors to mature red blood cells, and megaloblasts, which are abnormally large precursors that occur in megaloblastic anemias . Red blood cells are deformable, flexible, are able to adhere to other cells, and are able to interface with immune cells. Their membrane plays many roles in this. These functions are highly dependent on
9118-438: The tail binds to linker DNA and neutralizes its negative charge. Many experiments addressing H1 function have been performed on purified, processed chromatin under low-salt conditions, but H1's role in vivo is less certain. Cellular studies have shown that overexpression of H1 can cause aberrant nuclear morphology and chromatin structure, and that H1 can serve as both a positive and negative regulator of transcription, depending on
9215-405: The whole cell cycle. In mammals, genes encoding canonical histones are typically clustered along chromosomes in 4 different highly- conserved loci, lack introns and use a stem loop structure at the 3' end instead of a polyA tail . Genes encoding histone variants are usually not clustered, have introns and their mRNAs are regulated with polyA tails. Complex multicellular organisms typically have
9312-415: Was an increase in histone 3 lysine 9 acetylation in the pronociceptin promoter in the brain amygdala complex. This acetylation is an activating mark for pronociceptin. The nociceptin/nociceptin opioid receptor system is involved in the reinforcing or conditioning effects of alcohol. Methamphetamine addiction occurs in about 0.2% of the US population. Chronic methamphetamine use causes methylation of
9409-586: Was no consensus on the number of kinds of histone and that no one knew how they would compare when isolated from different organisms. Bonner and his collaborators then developed methods to separate each type of histone, purified individual histones, compared amino acid compositions in the same histone from different organisms, and compared amino acid sequences of the same histone from different organisms in collaboration with Emil Smith from UCLA. For example, they found Histone IV sequence to be highly conserved between peas and calf thymus. However, their work on
#605394