97-452: 5AX3 6774 20848 ENSG00000168610 ENSMUSG00000004040 P40763 P42227 NM_001369514 NM_001369516 NM_001369517 NM_001369518 NM_001369519 NM_001369520 NM_011486 NM_213659 NM_213660 NP_001356443 NP_001356445 NP_001356446 NP_001356447 NP_001356448 NP_001356449 NP_035616 NP_998824 NP_998825 Signal transducer and activator of transcription 3 ( STAT3 )
194-494: A strain of coronavirus known as "severe acute respiratory syndrome coronavirus 2" ( SARS-CoV-2 ). COVID-19 is mainly transmitted when people breathe in air contaminated by droplets / aerosols and small airborne particles containing the virus. Infected people exhale those particles as they breathe, talk, cough, sneeze, or sing. Transmission is more likely the closer people are. However, infection can occur over longer distances, particularly indoors. The transmission of
291-419: A certain critical size, generally thought to be <100μm diameter, evaporate faster than they settle; due to that fact, they form respiratory aerosol particles that remain airborne for a long period of time over extensive distances. Infectivity can begin four to five days before the onset of symptoms. Infected people can spread the disease even if they are pre-symptomatic or asymptomatic . Most commonly,
388-876: 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
485-439: 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
582-512: 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
679-646: A factor in metastasis of cancers. Hyperactivation of STAT3 occurs in COVID-19 infection and other viral infections. Loss-of-function mutations in the STAT3 gene result in hyperimmunoglobulin E syndrome , associated with recurrent infections as well as disordered bone and tooth development. Gain-of-function mutations in the STAT3 gene have been reported to cause multi-organ early onset auto-immune diseases; such as thyroid disease, diabetes, intestinal inflammation, and low blood counts, while constitutive STAT3 activation
776-452: 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
873-422: A higher risk of developing severe symptoms. Some complications result in death. Some people continue to experience a range of effects ( long COVID ) for months or years after infection, and damage to organs has been observed. Multi-year studies are underway to further investigate the long-term effects of the disease. COVID‑19 transmission occurs when infectious particles are breathed in or come into contact with
970-421: 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
1067-773: 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
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#17327726195081164-417: 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
1261-853: 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
1358-423: A range of effects, such as fatigue , for prolonged periods after an initial COVID-19 infection. This is the result of a condition called long COVID , which can be described as a range of persistent symptoms that continue for months or years. Long-term damage to organs has been observed after the onset of COVID-19. Multi-year studies are underway to further investigate the protracted effects of long COVID. Reducing
1455-452: 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,
1552-492: A tumor suppressor role depending upon the mutational background of the tumor. A direct connection between the PTEN-Akt-FOXO axis (suppressive) and the leukemia inhibitory factor receptor beta (LIFRbeta)-STAT3 signaling pathway (oncogenic) was shown. Increased activity of STAT3 in cancer cells, leads to changes in the function of protein complexes that control expression of inflammatory genes, with result profound change in
1649-419: 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
1746-744: Is a novel severe acute respiratory syndrome coronavirus. It was first isolated from three people with pneumonia connected to the cluster of acute respiratory illness cases in Wuhan. All structural features of the novel SARS-CoV-2 virus particle occur in related coronaviruses in nature, particularly in Rhinolophus sinicus (Chinese horseshoe bats). Outside the human body, the virus is destroyed by household soap which bursts its protective bubble . Hospital disinfectants, alcohols, heat, povidone-iodine , and ultraviolet -C (UV-C) irradiation are also effective disinfection methods for surfaces. SARS-CoV-2
1843-401: 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
1940-881: Is a transcription factor which in humans is encoded by the STAT3 gene . It is a member of the STAT protein family. STAT3 is a member of the STAT protein family. In response to cytokines and growth factors , STAT3 is phosphorylated by receptor-associated Janus kinases (JAK), forms homo- or heterodimers, and translocates to the cell nucleus where it acts as a transcription activator . Specifically, STAT3 becomes activated after phosphorylation of tyrosine 705 in response to such ligands as interferons , epidermal growth factor (EGF), interleukin (IL-)5 and IL-6 . Additionally, activation of STAT3 may occur via phosphorylation of serine 727 by mitogen-activated protein kinases (MAPK) and through c-src non-receptor tyrosine kinase. STAT3 mediates
2037-450: 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
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#17327726195082134-455: 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
2231-571: Is associated with COVID-19 and is reported in as many as 88% of symptomatic cases. Published data on the neuropathological changes related with COVID-19 have been limited and contentious, with neuropathological descriptions ranging from moderate to severe hemorrhagic and hypoxia phenotypes , thrombotic consequences, changes in acute disseminated encephalomyelitis (ADEM-type), encephalitis and meningitis . Many COVID-19 patients with co-morbidities have hypoxia and have been in intensive care for varying lengths of time, confounding interpretation of
2328-484: 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
2425-406: Is associated with various human cancers and commonly suggests poor prognosis. It has anti-apoptotic as well as proliferative effects. STAT3 can promote oncogenesis by being constitutively active through various pathways as mentioned elsewhere. A tumor suppressor role of STAT3 has also been reported. In the report on human glioblastoma tumor, or brain cancer, STAT3 was shown to have an oncogenic or
2522-595: 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
2619-433: Is available, guidelines and recommendations for hypertensive patients remain. The effect of the virus on ACE2 cell surfaces leads to leukocytic infiltration, increased blood vessel permeability, alveolar wall permeability, as well as decreased secretion of lung surfactants. These effects cause the majority of the respiratory symptoms. However, the aggravation of local inflammation causes a cytokine storm eventually leading to
2716-402: Is because pregnant women with COVID‑19 appear to be more likely to develop respiratory and obstetric complications that can lead to miscarriage , premature delivery and intrauterine growth restriction . Fungal infections such as aspergillosis , candidiasis , cryptococcosis and mucormycosis have been recorded in patients recovering from COVID‑19. COVID‑19 is caused by infection with
2813-442: 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
2910-522: Is closely related to the original SARS-CoV . It is thought to have an animal ( zoonotic ) origin. Genetic analysis has revealed that the coronavirus genetically clusters with the genus Betacoronavirus , in subgenus Sarbecovirus (lineage B) together with two bat-derived strains. It is 96% identical at the whole genome level to other bat coronavirus samples (BatCov RaTG13 ). The structural proteins of SARS-CoV-2 include membrane glycoprotein (M), envelope protein (E), nucleocapsid protein (N), and
3007-403: 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
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3104-409: 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
3201-414: 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,
3298-669: Is supplied to murine ESC cultures to maintain their undifferentiated state, can be omitted if STAT3 is activated through some other means. STAT3 is essential for the differentiation of the TH17 helper T cells, which have been implicated in a variety of autoimmune diseases . During viral infection, mice lacking STAT3 in T-cells display impairment in the ability to generate T-follicular helper (Tfh) cells and fail to maintain antibody based immunity. STAT3 caused upregulation in E-selectin,
3395-595: Is the cause of the bud release and the formation of the viral envelope. The N and E protein are accessory proteins that interfere with the host's immune response. Human angiotensin converting enzyme 2 (hACE2) is the host factor that SARS-CoV-2 virus targets causing COVID‑19. Theoretically, the usage of angiotensin receptor blockers (ARB) and ACE inhibitors upregulating ACE2 expression might increase morbidity with COVID‑19, though animal data suggest some potential protective effect of ARB; however no clinical studies have proven susceptibility or outcomes. Until further data
3492-469: Is the viral component that attaches to the host receptor via the ACE2 receptors. It includes two subunits: S1 and S2. Studies have shown that S1 domain induced IgG and IgA antibody levels at a much higher capacity. It is the focus spike proteins expression that are involved in many effective COVID‑19 vaccines. The M protein is the viral protein responsible for the transmembrane transport of nutrients. It
3589-938: The Alpha variant (B.1.1.7, formerly called the UK variant), first found in London and Kent, the Beta variant (B.1.351, formerly called the South Africa variant), the Gamma variant (P.1, formerly called the Brazil variant), the Delta variant (B.1.617.2, formerly called the India variant), and the Omicron variant (B.1.1.529), which had spread to 57 countries as of 7 December. On December 19, 2023,
3686-616: The SARS-CoV-1 and MERS-CoV outbreaks, and consistent with other pandemics in human history. Social and environmental factors including climate change , natural ecosystem destruction and wildlife trade increased the likelihood of such zoonotic spillover . The disease quickly spread worldwide, resulting in the COVID-19 pandemic . The symptoms of COVID‑19 are variable but often include fever, fatigue, cough, breathing difficulties , loss of smell , and loss of taste . Symptoms may begin one to fourteen days after exposure to
3783-588: The Spanish flu , Middle East respiratory syndrome , and Zika virus . In January 2020, the World Health Organization (WHO) recommended 2019-nCoV and 2019-nCoV acute respiratory disease as interim names for the virus and disease per 2015 guidance and international guidelines against using geographical locations or groups of people in disease and virus names to prevent social stigma . The official names COVID‑19 and SARS-CoV-2 were issued by
3880-514: 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
3977-920: 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
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4074-566: 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
4171-427: 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
4268-456: 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
4365-482: The small intestine . The virus can cause acute myocardial injury and chronic damage to the cardiovascular system . An acute cardiac injury was found in 12% of infected people admitted to the hospital in Wuhan, China, and is more frequent in severe disease. Rates of cardiovascular symptoms are high, owing to the systemic inflammatory response and immune system disorders during disease progression, but acute myocardial injuries may also be related to ACE2 receptors in
4462-710: The spike protein (S). The M protein of SARS-CoV-2 is about 98% similar to the M protein of bat SARS-CoV, maintains around 98% homology with pangolin SARS-CoV, and has 90% homology with the M protein of SARS-CoV; whereas, the similarity is only around 38% with the M protein of MERS-CoV . The many thousands of SARS-CoV-2 variants are grouped into either clades or lineages . The WHO, in collaboration with partners, expert networks, national authorities, institutions and researchers, have established nomenclature systems for naming and tracking SARS-CoV-2 genetic lineages by GISAID , Nextstrain and Pango . The expert group convened by
4559-548: The B.1 lineage. Several notable variants of SARS-CoV-2 emerged throughout 2020. Cluster 5 emerged among minks and mink farmers in Denmark . After strict quarantines and the slaughter of all the country's mink , the cluster was assessed to no longer be circulating among humans in Denmark as of 1 February 2021. As of December 2021 , there are five dominant variants of SARS-CoV-2 spreading among global populations:
4656-542: The CNS, possibly within an infected white blood cell. Research conducted when Alpha was the dominant variant has suggested COVID-19 may cause brain damage. Later research showed that all variants studied (including Omicron) killed brain cells, but the exact cells killed varied by variant. It is unknown if such damage is temporary or permanent. Observed individuals infected with COVID-19 (most with mild cases) experienced an additional 0.2% to 2% of brain tissue lost in regions of
4753-562: The COVID-19 infection may have different symptoms, and their symptoms may change over time. Three common clusters of symptoms have been identified: a respiratory symptom cluster with cough, sputum , shortness of breath , and fever; a musculoskeletal symptom cluster with muscle and joint pain, headache, and fatigue; and a cluster of digestive symptoms with abdominal pain, vomiting, and diarrhea. In people without prior ear, nose, or throat disorders, loss of taste combined with loss of smell
4850-431: 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
4947-411: 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
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#17327726195085044-430: 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
5141-475: The WHO declared that another distinctive variant, JN.1, had emerged as a "variant of interest". Though the WHO expected an increase in cases globally, particularly for countries entering winter, the overall global health risk was considered low. The SARS-CoV-2 virus can infect a wide range of cells and systems of the body. COVID‑19 is most known for affecting the upper respiratory tract (sinuses, nose, and throat) and
5238-759: The WHO on 11 February 2020 with COVID-19 being shorthand for "coronavirus disease 2019". The WHO additionally uses "the COVID‑19 virus" and "the virus responsible for COVID‑19" in public communications. The symptoms of COVID-19 are variable depending on the type of variant contracted, ranging from mild symptoms to a potentially fatal illness. Common symptoms include coughing , fever , loss of smell (anosmia) and taste (ageusia), with less common ones including headaches , nasal congestion and runny nose , muscle pain , sore throat , diarrhea , eye irritation , and toes swelling or turning purple, and in moderate to severe cases, breathing difficulties . People with
5335-551: The WHO recommended the labelling of variants using letters of the Greek alphabet , for example, Alpha , Beta , Delta , and Gamma , giving the justification that they "will be easier and more practical to discussed by non-scientific audiences". Nextstrain divides the variants into five clades (19A, 19B, 20A, 20B, and 20C), while GISAID divides them into seven (L, O, V, S, G, GH, and GR). The Pango tool groups variants into lineages , with many circulating lineages being classed under
5432-545: The actual proteins, some about their binding sites, or about their target genes. Examples include the following: COVID-19 Coronavirus disease 2019 ( COVID-19 ) is a contagious disease caused by the coronavirus SARS-CoV-2 . The first known case was identified in Wuhan , China, in December 2019. Most scientists believe the SARS-CoV-2 virus entered into human populations through natural zoonosis , similar to
5529-467: 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
5626-411: 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
5723-515: The brain connected to the sense of smell compared with uninfected individuals, and the overall effect on the brain was equivalent on average to at least one extra year of normal ageing; infected individuals also scored lower on several cognitive tests. All effects were more pronounced among older ages. The virus also affects gastrointestinal organs as ACE2 is abundantly expressed in the glandular cells of gastric , duodenal and rectal epithelium as well as endothelial cells and enterocytes of
5820-591: The brain found as complications leading to death in people infected with COVID‑19. Infection may initiate a chain of vasoconstrictive responses within the body, including pulmonary vasoconstriction – a possible mechanism in which oxygenation decreases during pneumonia. Furthermore, damage of arterioles and capillaries was found in brain tissue samples of people who died from COVID‑19. COVID‑19 may also cause substantial structural changes to blood cells , sometimes persisting for months after hospital discharge. A low level of blood lymphocytess may result from
5917-428: The brains of those who have died from COVID‑19, but these results need to be confirmed. While virus has been detected in cerebrospinal fluid of autopsies, the exact mechanism by which it invades the CNS remains unclear and may first involve invasion of peripheral nerves given the low levels of ACE2 in the brain. The virus may also enter the bloodstream from the lungs and cross the blood–brain barrier to gain access to
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#17327726195086014-450: 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
6111-409: The clear jelly liquid found in lung autopsies of people who died of COVID-19. One possibility addressed in medical research is that hyuralonic acid (HA) could be the leading factor for this observation of the clear jelly liquid found in the lungs, in what could be hyuralonic storm, in conjunction with cytokine storm . One common symptom, loss of smell, results from infection of the support cells of
6208-408: 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
6305-406: The data. Of people who show symptoms, 81% develop only mild to moderate symptoms (up to mild pneumonia ), while 14% develop severe symptoms ( dyspnea , hypoxia , or more than 50% lung involvement on imaging) that require hospitalization, and 5% of patients develop critical symptoms ( respiratory failure , septic shock , or multiorgan dysfunction ) requiring ICU admission. At least a third of
6402-653: 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
6499-721: The expression of ACE-2, thereby facilitating the SARS-Cov2 virus to enter cells and to replicate. A competition of negative feedback loops (via protective effects of interferon alpha) and positive feedback loops (via upregulation of ACE-2) is assumed to determine the fate of patients suffering from COVID-19. Additionally, people with COVID‑19 and acute respiratory distress syndrome (ARDS) have classical serum biomarkers of CRS, including elevated C-reactive protein (CRP), lactate dehydrogenase (LDH), D-dimer , and ferritin . Systemic inflammation results in vasodilation , allowing inflammatory lymphocytic and monocytic infiltration of
6596-411: The expression of a variety of genes in response to cell stimuli, and thus plays a key role in many cellular processes such as cell growth and apoptosis . STAT3-deficient mouse embryos cannot develop beyond embryonic day 7, when gastrulation begins. It appears that at these early stages of development, STAT3 activation is required for self-renewal of embryonic stem cells (ESCs). Indeed, LIF , which
6693-428: The eyes, nose, or mouth. The risk is highest when people are in close proximity, but small airborne particles containing the virus can remain suspended in the air and travel over longer distances, particularly indoors. Transmission can also occur when people touch their eyes, nose or mouth after touching surfaces or objects that have been contaminated by the virus. People remain contagious for up to 20 days and can spread
6790-525: The face. While drugs have been developed to inhibit the virus, the primary treatment is still symptomatic , managing the disease through supportive care , isolation , and experimental measures . During the initial outbreak in Wuhan , the virus and disease were commonly referred to as "coronavirus" and "Wuhan coronavirus", with the disease sometimes called "Wuhan pneumonia". In the past, many diseases have been named after geographical locations, such as
6887-535: 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
6984-469: 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
7081-523: The heart. ACE2 receptors are highly expressed in the heart and are involved in heart function. A high incidence of thrombosis and venous thromboembolism occurs in people transferred to intensive care units with COVID‑19 infections, and may be related to poor prognosis. Blood vessel dysfunction and clot formation (as suggested by high D-dimer levels caused by blood clots) may have a significant role in mortality, incidents of clots leading to pulmonary embolisms , and ischaemic events (strokes) within
7178-503: The host cell. Following viral entry, COVID‑19 infects the ciliated epithelium of the nasopharynx and upper airways. Autopsies of people who died of COVID‑19 have found diffuse alveolar damage , and lymphocyte-containing inflammatory infiltrates within the lung. From the CT scans of COVID-19 infected lungs, white patches were observed containing fluid known as ground-glass opacity (GGO) or simply ground glass. This tended to correlate with
7275-594: 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
7372-528: The infection, children may develop paediatric multisystem inflammatory syndrome , which has symptoms similar to Kawasaki disease , which can be fatal. In very rare cases, acute encephalopathy can occur, and it can be considered in those who have been diagnosed with COVID‑19 and have an altered mental status. According to the US Centers for Disease Control and Prevention , pregnant women are at increased risk of becoming seriously ill from COVID‑19. This
7469-454: The lower respiratory tract (windpipe and lungs). The lungs are the organs most affected by COVID‑19 because the virus accesses host cells via the receptor for the enzyme angiotensin-converting enzyme 2 (ACE2), which is most abundant on the surface of type II alveolar cells of the lungs. The virus uses a special surface glycoprotein called a " spike " to connect to the ACE2 receptor and enter
7566-409: The lung and the heart. In particular, pathogenic GM-CSF-secreting T cells were shown to correlate with the recruitment of inflammatory IL-6-secreting monocytes and severe lung pathology in people with COVID‑19. Lymphocytic infiltrates have also been reported at autopsy. Multiple viral and host factors affect the pathogenesis of the virus. The S-protein , otherwise known as the spike protein,
7663-447: The moment a person first becomes infected and the appearance of the first symptoms. The median delay for COVID-19 is four to five days possibly being infectious on 1–4 of those days. Most symptomatic people experience symptoms within two to seven days after exposure, and almost all will experience at least one symptom within 12 days. Most people recover from the acute phase of the disease. However, some people continue to experience
7760-432: 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
7857-530: 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
7954-415: 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
8051-480: The olfactory epithelium , with subsequent damage to the olfactory neurons . The involvement of both the central and peripheral nervous system in COVID‑19 has been reported in many medical publications. It is clear that many people with COVID-19 exhibit neurological or mental health issues . The virus is not detected in the central nervous system (CNS) of the majority of COVID-19 patients with neurological issues . However, SARS-CoV-2 has been detected at low levels in
8148-488: The peak viral load in upper respiratory tract samples occurs close to the time of symptom onset and declines after the first week after symptoms begin. Current evidence suggests a duration of viral shedding and the period of infectiousness of up to ten days following symptom onset for people with mild to moderate COVID-19, and up to 20 days for persons with severe COVID-19, including immunocompromised people. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
8245-411: The people who are infected with the virus do not develop noticeable symptoms at any point in time. These asymptomatic carriers tend not to get tested and can still spread the disease. Other infected people will develop symptoms later (called "pre-symptomatic") or have very mild symptoms and can also spread the virus. As is common with infections, there is a delay, or incubation period , between
8342-503: 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
8439-515: 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
8536-425: 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
8633-416: The respiratory tract, people with severe COVID‑19 have symptoms of systemic hyperinflammation. Clinical laboratory findings of elevated IL‑2 , IL‑6 , IL‑7 , as well as the following suggest an underlying immunopathology: Interferon alpha plays a complex, Janus-faced role in the pathogenesis of COVID-19. Although it promotes the elimination of virus-infected cells, it also upregulates
8730-859: The risk of long COVID includes staying up to date on the most recent COVID-19 vaccine, practicing good hygiene, maintaining clean indoor air, and physical distancing from people infected with a respiratory virus. Complications may include pneumonia , acute respiratory distress syndrome (ARDS), multi-organ failure , septic shock , and death. Cardiovascular complications may include heart failure, arrhythmias (including atrial fibrillation ), heart inflammation , thrombosis , particularly venous thromboembolism , and endothelial cell injury and dysfunction. Approximately 20–30% of people who present with COVID‑19 have elevated liver enzymes , reflecting liver injury. Neurologic manifestations include seizure , stroke, encephalitis , and Guillain–Barré syndrome (which includes loss of motor functions ). Following
8827-469: The secretome and the cell phenotypes, their activity in the tumor, and their capacity for metastasis. STAT3 has been shown to interact with: Niclosamide seems to inhibit the STAT3 signalling pathway. Nicotinamide (a type of vitamin B 3 ) naturally inhibits STAT3. However NAC ( Acetylcysteine ) inhibits STAT3 inhibitors. Transcription factor In molecular biology , a transcription factor ( TF ) (or sequence-specific DNA-binding factor )
8924-447: 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
9021-495: 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
9118-516: The virus acting through ACE2-related entry into lymphocytes. Another common cause of death is complications related to the kidneys . Early reports show that up to 30% of hospitalised patients both in China and in New York have experienced some injury to their kidneys, including some persons with no previous kidney problems. Although SARS-CoV-2 has a tropism for ACE2-expressing epithelial cells of
9215-752: The virus even if they do not develop symptoms. Testing methods for COVID-19 to detect the virus's nucleic acid include real-time reverse transcription polymerase chain reaction (RT‑PCR), transcription-mediated amplification , and reverse transcription loop-mediated isothermal amplification (RT‑LAMP) from a nasopharyngeal swab . Several COVID-19 vaccines have been approved and distributed in various countries, many of which have initiated mass vaccination campaigns . Other preventive measures include physical or social distancing , quarantining , ventilation of indoor spaces, use of face masks or coverings in public, covering coughs and sneezes, hand washing , and keeping unwashed hands away from
9312-509: The virus is carried out through virus-laden fluid particles, or droplets, which are created in the respiratory tract, and they are expelled by the mouth and the nose. There are three types of transmission: "droplet" and "contact", which are associated with large droplets, and "airborne", which is associated with small droplets. If the droplets are above a certain critical size, they settle faster than they evaporate , and therefore they contaminate surfaces surrounding them. Droplets that are below
9409-464: The virus. At least a third of people who are infected do not develop noticeable symptoms . Of those who develop symptoms noticeable enough to be classified as patients, most (81%) develop mild to moderate symptoms (up to mild pneumonia ), while 14% develop severe symptoms ( dyspnea , hypoxia , or more than 50% lung involvement on imaging), and 5% develop critical symptoms ( respiratory failure , shock , or multiorgan dysfunction ). Older people are at
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