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72-624: CREB-TF (CREB, cAMP response element-binding protein ) is a cellular transcription factor . It binds to certain DNA sequences called cAMP response elements (CRE), thereby increasing or decreasing the transcription of the genes . CREB was first described in 1987 as a cAMP -responsive transcription factor regulating the somatostatin gene. Genes whose transcription is regulated by CREB include: c-fos , BDNF , tyrosine hydroxylase , numerous neuropeptides (such as somatostatin , enkephalin , VGF , corticotropin-releasing hormone ), and genes involved in

144-876: 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

216-439: 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

288-476: A deficit in long-term, but not short-term, memory. Impairing CREB function did not impair retrieval of the consolidated memory. Small interfering RNA (siRNA) can induce a selective degradation of the mRNA of the protein of interest. Infusion of siRNA segments against CREB have produced deficits in both contextual conditioning and forward trace conditioning . A line of lacZ reporter mice (mice that have E. coli 's gene attached to their CREB gene to produce

360-503: 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

432-449: 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

504-421: 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

576-627: A line of mice with a targeted disruption of the α and δ isoforms of CREB showed intact short-term memory, but disrupted long-term memory in several behavioral tasks, including contextual conditioning and spatial learning in the Morris water maze , two hippocampal -dependent learning tasks. Also, hippocampal electrophysiological studies revealed that the CREB mutation disrupted the stability of synaptic plasticity Genetic studies in Drosophila fruit flies also uncovered

648-773: 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

720-532: A magnesium ion that facilitates binding to DNA. The cAMP response element (CRE) is the response element for CREB which contains the highly conserved nucleotide sequence, 5'-TGACGTCA-3’. CRE sites are typically found upstream of genes, within the promoter or enhancer regions. There are approximately 750,000 palindromic and half-site CREs in the human genome. However, the majority of these sites remain unbound due to cytosine methylation , which physically obstructs protein binding. A generalized sequence of events

792-417: A major role in determining sex in humans. Cells can communicate with each other by releasing molecules that produce signaling cascades within another receptive cell. If the signal requires upregulation or downregulation of genes in the recipient cell, often transcription factors will be downstream in the signaling cascade. Estrogen signaling is an example of a fairly short signaling cascade that involves

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864-853: 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

936-482: A protein that is easily visualized), when trained with a context protocol, showed higher levels of CREB-mediated transcription in the CA1 and CA3 regions of the hippocampus when compared to untrained mice or mice that did not associated content with shock (in fear conditioning) due to latent inhibition . Likewise, the lacZ mice that were trained with a tone protocol showed higher levels of CREB-dependent gene transcription in

1008-405: A result consistent with a role of the hippocampus in this form of conditioning. While viral CREB reversed the conditioning deficits in CREB knockout animals, additional CREB did not seem to enhance memory of the wild-type controls. Chronic enhancement of CREB, using genetic manipulations in mice, did not seem to enhance memory in a water maze task. Another 2009 study, which overexpressed CREB using

1080-445: A role for CREB in memory, suggesting that CREB has a role in memory conserved evolutionarily. There are several methods of knocking down (reducing the expression of) CREB: Antisense oligonucleotides (single strands of DNA or RNA that are complementary to a chosen sequence) against hippocampal CREB mRNA can lower levels of CREB within 6 hours of infusion and impair spatial memory. Tests given immediately after training showed that

1152-452: 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,

1224-419: 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

1296-401: 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

1368-447: 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

1440-405: Is also implicated in major depressive disorder. CREB is also thought to be involved in the growth of some types of cancer. Entrainment of the mammalian circadian clock is established via light induction of PER . Light excites melanopsin -containing photosensitive retinal ganglion cells which signal to the suprachiasmatic nucleus (SCN) via the retinohypothalamic tract (RHT). Excitation of

1512-455: 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

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1584-525: 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

1656-595: 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

1728-442: 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

1800-403: 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

1872-426: Is mediated via its basic leucine zipper domain ( bZIP domain ) as depicted in the image. Evidence suggests the β-adrenoceptor (a G-protein coupled receptor ) stimulates CREB signalling. CREB has many functions in many different organs, and some of its functions have been studied in relation to the brain. CREB proteins in neurons are thought to be involved in the formation of long-term memories; this has been shown in

1944-409: 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

2016-411: Is only significant during the subjective night. Michael Greenberg first demonstrated the role of CREB in the mammalian circadian clock in 1993 through a series of experiments that correlated phase-specific light pulses with CREB phosphorylation. In vitro, light during the subjective night increased phosphorylation of CREB rather than CREB protein levels. In vivo, phase shift-inducing light pulses during

2088-414: 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,

2160-514: Is summarized as follows: A signal arrives at the cell surface, activates the corresponding receptor, which leads to the production of a second messenger such as cAMP or Ca , which in turn activates a protein kinase . This protein kinase translocates to the cell nucleus , where it activates a CREB protein. The activated CREB protein then binds to a CRE region, and is then bound to by CBP (CREB-binding protein), which coactivates it, allowing it to switch certain genes on or off. The DNA binding of CREB

2232-507: 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

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2304-728: The amygdala than either mice with no training or mice in the unpaired group. There was no difference in CREB-dependent gene expression in the hippocampus of animals trained with a tone protocol. When a herpes simplex virus expressing CREB was infused into the amygdala of CREB knockout mice, the expression of CREB in the amygdala rescued the deficit, indicating that amygdal CREB is critical for memory in tone conditioning. The role of overexpression of CREB has not been examined systematically in fear conditioning, and studies of other conditioning paradigms has produced mixed results. A 2001 study, which used viral transfection to overexpress CREB in

2376-453: The basolateral amygdala of rats, found that overexpression increased the fear-potentiated startle response. This suggests that CREB levels are limiting during the acquisition of fear-potentiated startle and that these levels are related to the strength of this form of memory. A more recent paper (2009), using a similar viral approach in the hippocampus, found that additional CREB expression could also enhance contextual fear conditioning,

2448-526: The dentate gyrus behaved similarly to rats treated with antidepressants. From post-mortem examinations it has also been shown that the cortices of patients with untreated major depressive disorder contain reduced concentrations of CREB compared to both healthy controls and patients treated with antidepressants. The function of CREB can be modulated via a signalling pathway resulting from the binding of serotonin and noradrenaline to post-synaptic G-protein coupled receptors. Dysfunction of these neurotransmitters

2520-920: 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

2592-566: 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

2664-427: 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

2736-456: 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

2808-463: The tetracycline transgenic dox system , found that, while additional CREB did not enhance acquisition, it did interfere with memory retrieval, suggesting that there may be an optimal level of CREB activation for normal memory function. Other papers suggest that CREB helps control intrinsic excitability , providing an additional mechanism by which CREB can contribute to memory acquisition and expression. Enhanced CREB-dependent gene expression increases

2880-402: The DNA ; the transgenic protein lacks the domains required for making functional complexes. To regulate when the dominant negative CREB fragment interfered with normal CREB function, the mutant DNA was used to generate a fusion protein that also included a mutated ligand-binding domain (LBD) of the estrogen receptor , binding to tamoxifen rather than to estrogen . When exposed to tamoxifen,

2952-431: 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

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3024-411: 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

3096-430: 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

3168-499: The RHT signals the release of glutamate which is received by NMDA receptors on SCN, resulting in a calcium influx into the SCN. Calcium induces the activity of Ca/ calmodulin-dependent protein kinases , resulting in the activation of PKA , PKC , and CK2 . These kinases then phosphorylate CREB in a circadian manner that further regulates downstream gene expression. The phosphorylated CREB recognizes

3240-457: The Serine 133 residue. When activated, CREB protein recruits other transcriptional coactivators to bind to CRE promoter 5’ upstream region. Hydrophobic leucine amino acids are located along the inner edge of the alpha helix. These leucine residues tightly bind to leucine residues of another CREB protein forming a dimer. This chain of leucine residues forms the leucine zipper motif . The protein also has

3312-632: The actual proteins, some about their binding sites, or about their target genes. Examples include the following: CREB in Molecular and Cellular Cognition Research suggests that CREB has a role in the molecular steps that stabilize memory in the brain , including that of emotional memory . CREB modulates neuron excitability, meaning the propensity to generate an action potential upon receiving an input (crucial for long-term potentiation , LTP). Evidence of CREB's role in emotional memory falls into three experimental categories: negative manipulations (where

3384-467: 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

3456-441: The antisense oligonucleotides against CREB do not disrupt short-term memory. Another strategy for interfering with CREB function is the use of a dominant negative transgenic strategy. In this strategy, a fragment of the CREB gene was expressed from a transgene in mice. The resulting transgenic protein was engineered to interfere with the normal function of CREB by competing with wild type (non-mutated) CREB for binding sites in

3528-411: 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

3600-509: The brain can contribute to the development and progression of Huntington's disease . Abnormalities of a protein that interacts with the KID domain of CREB, the CREB-binding protein , (CBP) is associated with Rubinstein–Taybi syndrome . There is some evidence to suggest that the under-functioning of CREB is associated with major depressive disorder . Depressed rats with an overexpression of CREB in

3672-411: The cAMP Response Element and serves as a transcription factor for Per1 and Per2 , two genes that regulate the mammalian circadian clock. This induction of PER protein can entrain the circadian clock to light/dark cycles inhibits its own transcription via a transcription-translation feedback loop which can advance or delay the circadian clock. However, the responsiveness of PER1 and PER2 protein induction

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3744-447: 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

3816-408: 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

3888-522: The dominant negative fragment changed the conformation of the fusion protein, became active, and could therefore interfere with CREB binding sites. One advantage of this inducible transgenic system is that the altered protein is constitutively present and can therefore be rapidly activated following the administration of tamoxifen. Use of the LBD system to knock down CREB protein function during training (using both contextual freezing and tone fear paradigms) produced

3960-647: 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

4032-475: The formation of spatial memory . CREB downregulation is implicated in the pathology of Alzheimer's disease and increasing the expression of CREB is being considered as a possible therapeutic target for Alzheimer's disease. CREB also has a role in photoentrainment in mammals. The following genes encode CREB or CREB-like proteins: CREB proteins are activated by phosphorylation from various kinases, including PKA , and Ca/calmodulin-dependent protein kinases on

4104-535: 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

4176-469: 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

4248-594: 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

4320-416: The inactive form of CREB lose their ability to retain long-term memory. CREB is also important for the survival of neurons, as shown in genetically engineered mice, where CREB and CREM were deleted in the brain. If CREB is lost in the whole developing mouse embryo, the mice die immediately after birth, again highlighting the critical role of CREB in promoting neuronal survival. Disturbance of CREB function in

4392-528: The levels of CREB were lowered), positive manipulations (where the levels of CREB were increased), and non-interventions (where the endogenous levels of CREB were tracked before and after learning). Knockout studies in Aplysia sea slugs indicated that decreasing CREB function blocks long-term changes in synaptic function, but not short-term ones. Changes in synaptic function (i.e., synaptic plasticity ) are required for learning and memory As evidence of this,

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4464-410: The mammalian circadian clock ( PER1 , PER2 ). CREB is closely related in structure and function to CREM ( cAMP response element modulator ) and ATF-1 ( activating transcription factor-1 ) proteins. CREB proteins are expressed in many animals, including humans. CREB has a well-documented role in neuronal plasticity and long-term memory formation in the brain and has been shown to be integral in

4536-422: The marine snail Aplysia , the fruit fly Drosophila melanogaster , in rats and in mice (see CREB in Molecular and Cellular Cognition ). CREB is necessary for the late stage of long-term potentiation . CREB also has an important role in the development of drug addiction and even more so in psychological dependence . There are activator and repressor forms of CREB. Flies genetically engineered to overexpress

4608-432: 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

4680-530: 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

4752-415: 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

4824-503: 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

4896-509: 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

4968-425: 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

5040-517: The subjective night correlated with CREB phosphorylation in the SCN. Experiments by Gunther Schutz in 2002 demonstrated that mutant mice lacking the Ser142 phosphorylation site failed to induce the clock regulatory gene mPer1 in response to a light pulse. Furthermore, these mutant mice had difficulty entraining to light-dark cycles. Transcription factor In molecular biology , a transcription factor ( TF ) (or sequence-specific DNA-binding factor )

5112-447: 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

5184-495: 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

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