Editing Transcription factor (section)

== Structure ==
[[File:Transcription factor schematic 2.png|thumb|upright=1.75|Schematic diagram of the amino acid sequence (amino terminus to the left and carboxylic acid terminus to the right) of a prototypical transcription factor that contains (1) a DNA-binding domain (DBD), (2) signal-sensing domain (SSD), and Activation domain (AD). The order of placement and the number of domains may differ in various types of transcription factors. In addition, the transactivation and signal-sensing functions are frequently contained within the same domain.]]

[[File:LacI Dimer Structure Annotated.png|thumb|upright=1.25|'''Domain architecture example: [[lac repressor|Lactose Repressor (LacI)]]'''.  The N-terminal DNA binding domain (labeled) of the [[lac repressor|''lac'' repressor]] binds its target DNA sequence (gold) in the major groove using a [[helix-turn-helix]] motif. Effector molecule binding (green) occurs in the regulatory domain (labeled).  This triggers an allosteric response mediated by the linker region (labeled).]]

Transcription factors are modular in structure and contain the following [[protein domains|domains]]:<ref name="pmid9570129" />
* '''[[DNA-binding domain]]''' ('''DBD'''), which attaches to specific sequences of DNA ([[enhancer (genetics)|enhancer]] or [[promoter (biology)|promoter]]. Necessary component for all vectors. Used to drive transcription of the vector's transgene [[promoter (biology)|promoter]] sequences) adjacent to regulated genes.  DNA sequences that bind transcription factors are often referred to as '''[[hormone response element|response elements]]'''.
* '''[[Trans-activating domain|Activation domain]]''' ('''AD'''), which contains binding sites for other proteins such as [[transcription coregulator]]s.  These binding sites are frequently referred to as '''activation functions''' ('''AFs'''), '''Transactivation domain''' ('''TAD''') or '''Trans-activating domain''' [[Trans-activating domain|TAD]], not to be confused with topologically associating domain ([[Topologically associating domain|TAD]]).<ref name="pmid12893880">{{Cite journal |vauthors=Wärnmark A, Treuter E, Wright AP, Gustafsson JA |date=October 2003 |title=Activation functions 1 and 2 of nuclear receptors: molecular strategies for transcriptional activation |journal=Molecular Endocrinology |volume=17 |issue=10 |pages=1901–9 |doi=10.1210/me.2002-0384 |pmid=12893880 |s2cid=31314461 |doi-access=free}}</ref>
*  An optional '''signal-sensing domain''' ('''SSD''') (''e.g.'', a ligand-binding domain), which senses external signals and, in response, transmits these signals to the rest of the transcription complex, resulting in up- or down-regulation of gene expression.  Also, the DBD and signal-sensing domains may reside on separate proteins that associate within the transcription complex to regulate gene expression.

=== DNA-binding domain ===
[[File:Transcription factors DNA binding sites.svg|thumb|right|DNA contacts of different types of [[w:DNA-binding domain|DNA-binding domains]] of transcription factors]]

{{Main|DNA-binding domain}}
The portion ([[protein domains|domain]]) of the transcription factor that binds DNA is called its DNA-binding domain.  Below is a partial list of some of the major families of DNA-binding domains/transcription factors:

{| class="wikitable"
|-
! style="width:300pt;"| Family
! style="width:100pt;"| [[InterPro]]
! style="width:100pt;"| [[Pfam]]
! style="width:100pt;"| [[Structural Classification of Proteins|SCOP]]
|-
| [[basic helix-loop-helix]]<ref name="pmid7553065">{{Cite journal |vauthors=Littlewood TD, Evan GI |year=1995 |title=Transcription factors 2: helix-loop-helix |journal=Protein Profile |volume=2 |issue=6 |pages=621–702 |pmid=7553065}}</ref>
| {{InterPro|IPR001092}}
| {{Pfam|PF00010}}
| {{SCOP|47460}}
|-
| basic-leucine zipper ([[bZIP domain|bZIP]])<ref name="pmid12192032">{{Cite journal |vauthors=Vinson C, Myakishev M, Acharya A, Mir AA, Moll JR, Bonovich M |date=September 2002 |title=Classification of human B-ZIP proteins based on dimerization properties |journal=Molecular and Cellular Biology |volume=22 |issue=18 |pages=6321–35 |doi=10.1128/MCB.22.18.6321-6335.2002 |pmc=135624 |pmid=12192032}}</ref>
| {{InterPro|IPR004827}}
| {{Pfam|PF00170}}
| {{SCOP|57959}}
|-
| C-terminal effector domain of the bipartite response regulators
| {{InterPro|IPR001789}}
| {{Pfam|PF00072}}
| {{SCOP|46894}}
|-
| AP2/ERF/GCC box
| {{InterPro|IPR001471}}
| {{Pfam|PF00847}}
| {{SCOP|54176}}
|-
| [[helix-turn-helix]]<ref name="pmid8831795">{{Cite journal |vauthors=Wintjens R, Rooman M |date=September 1996 |title=Structural classification of HTH DNA-binding domains and protein-DNA interaction modes |journal=Journal of Molecular Biology |volume=262 |issue=2 |pages=294–313 |doi=10.1006/jmbi.1996.0514 |pmid=8831795}}</ref>
|
|
|
|-
| [[homeodomain fold|homeodomain proteins]], which are encoded by [[homeobox]] genes, are transcription factors.  Homeodomain proteins play critical roles in the regulation of [[developmental biology|development]].<ref name="pmid7979246">{{Cite journal |vauthors=Gehring WJ, Affolter M, Bürglin T |year=1994 |title=Homeodomain proteins |journal=Annual Review of Biochemistry |volume=63 |pages=487–526 |doi=10.1146/annurev.bi.63.070194.002415 |pmid=7979246}}</ref><ref name="pmid 26464018">{{Cite journal |vauthors=Bürglin TR, Affolter M |date=June 2016 |title=Homeodomain proteins: an update |journal=Chromosoma |volume=125 |issue=3 |pages=497–521 |doi=10.1007/s00412-015-0543-8 |pmc=4901127 |pmid=26464018}}</ref>
| {{InterPro|IPR009057}}
| {{Pfam|PF00046}}
| {{SCOP|46689}}
|-
| [[CI protein|lambda repressor]]-like
| {{InterPro|IPR010982}}
|
| {{SCOP|47413}}
|-
| srf-like ([[serum response factor]])
| {{InterPro|IPR002100}}
| {{Pfam|PF00319}}
| {{SCOP|55455}}
|-
| [[pax genes|paired box]]<ref name="pmid9297966">{{Cite journal |vauthors=Dahl E, Koseki H, Balling R |date=September 1997 |title=Pax genes and organogenesis |journal=BioEssays |volume=19 |issue=9 |pages=755–65 |doi=10.1002/bies.950190905 |pmid=9297966 |s2cid=23755557}}</ref>
|
|
|
|-
| [[winged helix]]
| {{InterPro|IPR013196}}
| {{Pfam|PF08279}}
| {{SCOP|46785}}
|-
| [[zinc finger]]s<ref name="pmid11179890">{{Cite journal |vauthors=Laity JH, Lee BM, Wright PE |date=February 2001 |title=Zinc finger proteins: new insights into structural and functional diversity |journal=Current Opinion in Structural Biology |volume=11 |issue=1 |pages=39–46 |doi=10.1016/S0959-440X(00)00167-6 |pmid=11179890}}</ref>
|
|
|
|-
| * multi-domain Cys<sub>2</sub>His<sub>2</sub> zinc fingers<ref name="pmid10940247">{{Cite journal |vauthors=Wolfe SA, Nekludova L, Pabo CO |year=2000 |title=DNA recognition by Cys2His2 zinc finger proteins |journal=Annual Review of Biophysics and Biomolecular Structure |volume=29 |pages=183–212 |doi=10.1146/annurev.biophys.29.1.183 |pmid=10940247}}</ref>
| {{InterPro|IPR007087}}
| {{Pfam|PF00096}}
| {{SCOP|57667}}
|-
| * Zn<sub>2</sub>/Cys<sub>6</sub>
|
|
| {{SCOP|57701}}
|-
| * Zn<sub>2</sub>/Cys<sub>8</sub> [[nuclear receptor]] zinc finger
| {{InterPro|IPR001628}}
| {{Pfam|PF00105}}
| {{SCOP|57716}}
|}

=== Response elements ===

The DNA sequence that a transcription factor binds to is called a [[transcription factor-binding site]] or [[response element]].<ref name="pmid15711128">{{Cite journal |vauthors=Wang JC |date=March 2005 |title=Finding primary targets of transcriptional regulators |url=http://www.landesbioscience.com/journals/cc/abstract.php?id=1521 |journal=Cell Cycle |volume=4 |issue=3 |pages=356–8 |doi=10.4161/cc.4.3.1521 |pmid=15711128 |doi-access=free}}</ref>

Transcription factors interact with their binding sites using a combination of [[Coulomb's law|electrostatic]] (of which [[hydrogen bond]]s are a special case) and [[Van der Waals force]]s.  Due to the nature of these chemical interactions, most transcription factors bind DNA in a sequence specific manner.  However, not all [[Base pair|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 a different strength of interaction.{{cn|date=March 2024}}

For example, although the [[consensus sequence|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.{{cn|date=March 2024}}

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 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 (biology)|cell]].  Other constraints, such as DNA accessibility in the cell or availability of [[cofactor (biochemistry)|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 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.