Editing Transcription factor (section)

== Function ==

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 the important functions and biological roles transcription factors are involved in:

=== Basal transcriptional regulation ===

In [[eukaryote]]s, an important class of transcription factors called [[general transcription factor]]s (GTFs) are necessary for transcription to occur.<ref name="isbn1-86094-126-5">{{Cite book | vauthors = Weinzierl RO |url=https://archive.org/details/mechanismsofgene0000wein |title=Mechanisms of Gene Expression: Structure, Function and Evolution of the Basal Transcriptional Machinery |publisher=World Scientific Publishing Company |year=1999 |isbn=1-86094-126-5 |url-access=registration}}</ref><ref name="pmid12672487">{{Cite journal |vauthors=Reese JC |date=April 2003 |title=Basal transcription factors |journal=Current Opinion in Genetics & Development |volume=13 |issue=2 |pages=114–8 |doi=10.1016/S0959-437X(03)00013-3 |pmid=12672487}}</ref><ref name="pmid12676794">{{Cite journal |vauthors=Shilatifard A, Conaway RC, Conaway JW |year=2003 |title=The RNA polymerase II elongation complex |journal=Annual Review of Biochemistry |volume=72 |pages=693–715 |doi=10.1146/annurev.biochem.72.121801.161551 |pmid=12676794}}</ref>  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]].<ref name="pmid16858867">{{Cite journal |vauthors=Thomas MC, Chiang CM |year=2006 |title=The general transcription machinery and general cofactors |journal=Critical Reviews in Biochemistry and Molecular Biology |volume=41 |issue=3 |pages=105–78 |doi=10.1080/10409230600648736 |pmid=16858867 |s2cid=13073440}}</ref>  The preinitiation complex binds to [[promotor (biology)|promoter]] regions of DNA upstream to the gene that they regulate.

=== Differential enhancement of transcription ===
Other transcription factors differentially regulate the expression of various genes by binding to [[enhancer (genetics)|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.{{cn|date=March 2024}}

==== Development ====

Many transcription factors in [[multicellular organism]]s are involved in development.<ref name="pmid1424766">{{Cite book |title=Transcription factors and mammalian development |vauthors=Lobe CG |year=1992 |isbn=978-0-12-153127-0 |series=Current Topics in Developmental Biology |volume=27 |pages=351–83 |doi=10.1016/S0070-2153(08)60539-6 |pmid=1424766}}</ref>  Responding to stimuli, these transcription factors turn on/off the transcription of the appropriate genes, which, in turn, allows for changes in cell [[morphology (biology)|morphology]] or activities needed for [[cell fate determination]] and [[cellular differentiation]].  The [[Hox (gene)|Hox]] transcription factor family, for example, is important for proper [[Regional specification|body pattern formation]] in organisms as diverse as fruit flies to humans.<ref name="pmid17008523">{{Cite journal |vauthors=Lemons D, McGinnis W |date=September 2006 |title=Genomic evolution of Hox gene clusters |journal=Science |volume=313 |issue=5795 |pages=1918–22 |bibcode=2006Sci...313.1918L |doi=10.1126/science.1132040 |pmid=17008523 |s2cid=35650754}}</ref><ref name="pmid16515781">{{Cite journal |author-link=Cecilia Moens |vauthors=Moens CB, Selleri L |date=March 2006 |title=Hox cofactors in vertebrate development |journal=Developmental Biology |volume=291 |issue=2 |pages=193–206 |doi=10.1016/j.ydbio.2005.10.032 |pmid=16515781 |doi-access=free}}</ref>  Another example is the transcription factor encoded by the [[SRY|sex-determining region Y]] (SRY) gene, which plays a major role in determining sex in humans.<ref name="pmid17187356">{{Cite journal |vauthors=Ottolenghi C, Uda M, Crisponi L, Omari S, Cao A, Forabosco A, Schlessinger D |date=January 2007 |title=Determination and stability of sex |journal=BioEssays |volume=29 |issue=1 |pages=15–25 |doi=10.1002/bies.20515 |pmid=17187356 |hdl=11380/611683 |s2cid=23824870}}</ref>

==== Response to intercellular signals ====

Cells can communicate with each other by releasing molecules that produce [[signal transduction|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.<ref name="pmid8293575">{{Cite journal |vauthors=Pawson T |year=1993 |title=Signal transduction--a conserved pathway from the membrane to the nucleus |journal=Developmental Genetics |volume=14 |issue=5 |pages=333–8 |doi=10.1002/dvg.1020140502 |pmid=8293575}}</ref> [[Estrogen]] signaling is an example of a fairly short signaling cascade that involves the [[estrogen receptor]] transcription factor:  Estrogen is secreted by tissues such as the [[ovary|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 [[Cell nucleus|nucleus]] and binds to its [[DNA binding site|DNA-binding sites]], changing the transcriptional regulation of the associated genes.<ref name="pmid11916222">{{Cite journal |vauthors=Osborne CK, Schiff R, Fuqua SA, Shou J |date=December 2001 |title=Estrogen receptor: current understanding of its activation and modulation |journal=Clinical Cancer Research |volume=7 |issue=12 Suppl |pages=4338s–4342s; discussion 4411s–4412s |pmid=11916222}}</ref>

==== Response to environment ====

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,<ref name="pmid18239856">{{Cite journal |vauthors=Shamovsky I, Nudler E |date=March 2008 |title=New insights into the mechanism of heat shock response activation |journal=Cellular and Molecular Life Sciences |volume=65 |issue=6 |pages=855–61 |doi=10.1007/s00018-008-7458-y |pmc=11131843 |pmid=18239856 |s2cid=9912334}}</ref> [[hypoxia inducible factor]] (HIF), which upregulates genes necessary for cell survival in low-oxygen environments,<ref name="pmid18202826">{{Cite journal |vauthors=Benizri E, Ginouvès A, Berra E |date=April 2008 |title=The magic of the hypoxia-signaling cascade |journal=Cellular and Molecular Life Sciences |volume=65 |issue=7–8 |pages=1133–49 |doi=10.1007/s00018-008-7472-0 |pmc=11131810 |pmid=18202826 |s2cid=44049779}}</ref> and [[sterol regulatory element binding protein]] (SREBP), which helps maintain proper [[lipid]] levels in the cell.<ref name="pmid15457548">{{Cite journal |vauthors=Weber LW, Boll M, Stampfl A |date=November 2004 |title=Maintaining cholesterol homeostasis: sterol regulatory element-binding proteins |journal=World Journal of Gastroenterology |volume=10 |issue=21 |pages=3081–7 |doi=10.3748/wjg.v10.i21.3081 |pmc=4611246 |pmid=15457548 |doi-access=free}}</ref>

==== Cell cycle control ====

Many transcription factors, especially some that are [[proto-oncogene]]s or [[tumor suppressor gene|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.<ref name="pmid8960358">{{Cite journal |vauthors=Wheaton K, Atadja P, Riabowol K |year=1996 |title=Regulation of transcription factor activity during cellular aging |journal=Biochemistry and Cell Biology |volume=74 |issue=4 |pages=523–34 |doi=10.1139/o96-056 |pmid=8960358}}</ref><ref name="pmid8864058">{{Cite journal |vauthors=Meyyappan M, Atadja PW, Riabowol KT |year=1996 |title=Regulation of gene expression and transcription factor binding activity during cellular aging |journal=Biological Signals |volume=5 |issue=3 |pages=130–8 |doi=10.1159/000109183 |pmid=8864058}}</ref>  One example is the [[Myc]] oncogene, which has important roles in [[cell growth]] and [[apoptosis]].<ref name="pmid7846125">{{Cite journal |vauthors=Evan G, Harrington E, Fanidi A, Land H, Amati B, Bennett M |date=August 1994 |title=Integrated control of cell proliferation and cell death by the c-myc oncogene |journal=Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences |volume=345 |issue=1313 |pages=269–75 |bibcode=1994RSPTB.345..269E |doi=10.1098/rstb.1994.0105 |pmid=7846125}}</ref>

==== Pathogenesis ====

Transcription factors can also be used to alter gene expression in a host cell to promote pathogenesis.  A well studied example of this are the transcription-activator like effectors ([[TAL effector]]s) 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.<ref name="Boch J, Bonas U. 2010">{{Cite journal |vauthors=Boch J, Bonas U |year=2010 |title=Xanthomonas AvrBs3 family-type III effectors: discovery and function |journal=Annual Review of Phytopathology |volume=48 |issue=1 |pages=419–36 |doi=10.1146/annurev-phyto-080508-081936 |pmid=19400638|bibcode=2010AnRvP..48..419B }}</ref> TAL effectors contain a central repeat region in which there 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.<ref name="Moscou2010">{{Cite journal |vauthors=Moscou MJ, Bogdanove AJ |date=December 2009 |title=A simple cipher governs DNA recognition by TAL effectors |journal=Science |volume=326 |issue=5959 |pages=1501 |bibcode=2009Sci...326.1501M |doi=10.1126/science.1178817 |pmid=19933106 |s2cid=6648530}}</ref><ref name="Boch J, Scholze H, Schornack S, ''et al.'' 2010">{{Cite journal |vauthors=Boch J, Scholze H, Schornack S, Landgraf A, Hahn S, Kay S, Lahaye T, Nickstadt A, Bonas U |date=December 2009 |title=Breaking the code of DNA binding specificity of TAL-type III effectors |journal=Science |volume=326 |issue=5959 |pages=1509–12 |bibcode=2009Sci...326.1509B |doi=10.1126/science.1178811 |pmid=19933107 |s2cid=206522347}}</ref> This property likely makes it easier for these proteins to evolve in order to better compete with the defense mechanisms of the host cell.<ref name="Voytas DF, Joung JK. 2010.">{{Cite journal |vauthors=Voytas DF, Joung JK |date=December 2009 |title=Plant science. DNA binding made easy |journal=Science |volume=326 |issue=5959 |pages=1491–2 |bibcode=2009Sci...326.1491V |doi=10.1126/science.1183604 |pmc=7814878 |pmid=20007890 |s2cid=33257689}}</ref>