Editing DNA-binding protein (section)

==Binding to specific DNA sequences==
[[File:Transcription factors DNA binding sites.svg|thumb|right|DNA contacts of different types of DNA-binding domains from transcription factors]]
In contrast, other proteins have evolved to bind to specific DNA sequences. The most intensively studied of these are the various [[transcription factor]]s, which are proteins that regulate transcription. Each transcription factor binds to one specific set of DNA sequences and activates or inhibits the transcription of genes that have these sequences near their promoters. The transcription factors do this in two ways. Firstly, they can bind the RNA polymerase responsible for transcription, either directly or through other mediator proteins; this locates the polymerase at the promoter and allows it to begin transcription.<ref>{{cite journal |vauthors=Myers L, Kornberg R |title=Mediator of transcriptional regulation |journal=Annu Rev Biochem |volume=69 |issue=1 |pages=729–49 |year=2000 |pmid=10966474 |doi= 10.1146/annurev.biochem.69.1.729}}</ref> Alternatively, transcription factors can bind [[enzyme]]s that modify the histones at the promoter. This alters the accessibility of the DNA template to the polymerase.<ref>{{cite journal |vauthors=Spiegelman B, Heinrich R |title=Biological control throughs regulated transcriptional coactivators |journal=Cell |volume=119 |issue=2 |pages=157–67 |year=2004 |pmid=15479634 |doi=10.1016/j.cell.2004.09.037|s2cid=14668705 |doi-access=free }}</ref>

These DNA targets can occur throughout an organism's genome. Thus, changes in the activity of one type of transcription factor can affect thousands of genes.<ref>{{cite journal |vauthors=Li Z, Van Calcar S, Qu C, Cavenee W, Zhang M, Ren B |title=A global transcriptional regulatory role for c-Myc in Burkitt's lymphoma cells |journal=Proc Natl Acad Sci USA |volume=100 |issue=14 |pages=8164–9 |year=2003 |pmid=12808131 |doi= 10.1073/pnas.1332764100 |pmc=166200|bibcode=2003PNAS..100.8164L |doi-access=free }}</ref> Thus, these proteins are often the targets of the [[signal transduction]] processes that control responses to environmental changes or [[cellular differentiation]] and development. The specificity of these transcription factors' interactions with DNA come from the proteins making multiple contacts to the edges of the DNA bases, allowing them to ''read'' the DNA sequence. Most of these base-interactions are made in the major groove, where the bases are most accessible.<ref>{{cite journal |vauthors=Pabo C, Sauer R |title=Protein-DNA recognition |journal=Annu Rev Biochem |volume=53 |issue=1 |pages=293–321 |year=1984 |pmid=6236744 |doi= 10.1146/annurev.bi.53.070184.001453}}</ref> Mathematical descriptions of protein-DNA binding taking into account sequence-specificity, and competitive and cooperative binding of proteins of different types are usually performed with the help of the [[lattice model (biophysics)|lattice models]].<ref>{{cite journal |author=Teif V.B. |author2=Rippe K. |title=Statistical-mechanical lattice models for protein-DNA binding in chromatin. |journal=Journal of Physics: Condensed Matter|year=2010|arxiv=1004.5514|doi=10.1088/0953-8984/22/41/414105 |pmid=21386588 |volume=22 |issue=41 |pages=414105|bibcode=2010JPCM...22O4105T|s2cid=103345 }}</ref> Computational methods to identify the DNA binding sequence specificity have been proposed to make a good use of the abundant sequence data in the post-genomic era.<ref>{{cite journal | vauthors = Wong KC, Chan TM, Peng C, Li Y, Zhang Z | year = 2013 | title = DNA Motif Elucidation using belief propagation | url= | journal = Nucleic Acids Research | volume =  41| issue = 16| page =  e153| doi = 10.1093/nar/gkt574 | pmid = 23814189 | pmc = 3763557 }}</ref> In addition, progress has happened on  structure-based prediction of binding specificity across protein families using deep learning.<ref>{{Cite journal |last1=Mitra |first1=Raktim |last2=Li |first2=Jinsen |last3=Sagendorf |first3=Jared M. |last4=Jiang |first4=Yibei |last5=Cohen |first5=Ari S. |last6=Chiu |first6=Tsu-Pei |last7=Glasscock |first7=Cameron J. |last8=Rohs |first8=Remo |date=2024-08-05 |title=Geometric deep learning of protein–DNA binding specificity |journal=Nature Methods |volume=21 |issue=9 |pages=1674–1683 |language=en |doi=10.1038/s41592-024-02372-w |issn=1548-7091|doi-access=free |pmid=39103447 |pmc=11399107 }}</ref>