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{{Short description|Regulatory DNA sequences}}
'''Distal promoter''' elements are [[regulatory sequence|regulatory DNA sequences]] that can be many kilobases distant from the [[gene]] that they regulate.<ref name="r1">{{cite journal | vauthors = Roeder RG | title = The complexities of eukaryotic transcription initiation: regulation of preinitiation complex assembly | journal = Trends in Biochemical Sciences | volume = 16 | issue = 11 | pages = 402–408 | date = November 1991 | pmid = 1776168 | doi = 10.1016/0968-0004(91)90164-Q }}</ref>

They can either be [[Enhancer (genetics)|enhancer]]s (increasing expression) or [[Silencer (genetics)|silencer]]s (decreasing expression). They act by binding [[Activator (genetics)|activator]] or [[Repressor (genetics)|repressor]] proteins ([[transcription factor]]s) and the intervening DNA bends such that the bound proteins contact the [[core promoter]] and [[RNA polymerase]].<ref name="r1" />

== In T-cell development ==

T-cell development and activation is controlled by complementary placement of proximal and distal ''lck'' promoters. The generated environment of a Lck-PROX mice when approached with proximal promoter demonstrates maximal ''lck'' protein and normal thymic development, while distal promoters lead to deficient ''lck'' protein and unnormal thymic levels.<ref>{{cite journal | vauthors = Chiang YJ, Hodes RJ | title = T-cell development is regulated by the coordinated function of proximal and distal Lck promoters active at different developmental stages | journal = European Journal of Immunology | volume = 46 | issue = 10 | pages = 2401–2408 | date = October 2016 | pmid = 27469439 | pmc = 5183457 | doi = 10.1002/eji.201646440 }}</ref>

Further research at the late stage of thymocyte development reveals that distal Lck promoter with driven Cre will result in the distal ''lck'' gene promoter to drive Cre expression to be limited within innate-like T cells. There is a cell type specific function in innate-like T cells based on the distal ''lck'' promoter - driven Cre.<ref>{{cite journal | vauthors = Figueroa MG, Parker LM, Krol K, Zhao M | title = Distal ''Lck'' Promoter-Driven Cre Shows Cell Type-Specific Function in Innate-like T Cells | journal = ImmunoHorizons | volume = 5 | issue = 9 | pages = 772–781 | date = September 2021 | pmid = 34583938 | pmc = 8612026 | doi = 10.4049/immunohorizons.2100079 }}</ref>

== In cancer ==
Multiple studies have discovered abnormalities in distal promoters within cancer cells. For example, an overactive distal promoter located about 1 kilobase away from the MUC5B gene contributes to atypical expression of this gene in gastric cancer cells.<ref>{{Cite journal |last1=Perrais |first1=Michaël |last2=Pigny |first2=Pascal |last3=Buisine |first3=Marie-Pierre |last4=Porchet |first4=Nicole |last5=Aubert |first5=Jean-Pierre |last6=Seuningen-Lempire |first6=Isabelle Van |date=2001-01-01 |title=Aberrant Expression of Human Mucin GeneMUC5B in Gastric Carcinoma and Cancer Cells: IDENTIFICATION AND REGULATION OF A DISTAL PROMOTER * |journal=Journal of Biological Chemistry |language=English |volume=276 |issue=18 |pages=15386–15396 |doi=10.1074/jbc.M010534200 |doi-access=free |pmid=11278696 |issn=0021-9258}}</ref> Similarly, a few polymorphisms in the RUNX3 distal promoter alter the promoter's function, increasing the activity of the NF-κB transcription factor and the expression of the IL1B gene. These polymorphisms have been correlated with increased vulnerability to intestinal gastric cancer.<ref>{{Cite journal |last1=Lim |first1=Byungho |last2=Ju |first2=Hyoungseok |last3=Kim |first3=Minjin |last4=Kang |first4=Changwon |date=2011 |title=Increased genetic susceptibility to intestinal-type gastric cancer is associated with increased activity of the RUNX3 distal promoter |url=https://acsjournals.onlinelibrary.wiley.com/doi/10.1002/cncr.26161 |journal=Cancer |language=en |volume=117 |issue=22 |pages=5161–5171 |doi=10.1002/cncr.26161 |pmid=21523770 |issn=1097-0142}}</ref>

Another cancer- related gene is EGLN2, which is located in the chromosome (19q13.2 region). This gene encodes an enzyme that can recognize conserved prolyl residues and hydroxylates it in a α-subunit of hypoxia inducible factor (HIF). The functional polymorphism is a 4bp insertion/deletion within the distal promoters, which can affect the expression of EGLN2.<ref>{{cite journal |last1=Zhang |first1=Shulong |last2=Zhu |first2=Kaihua |last3=Zhang |first3=Zuoliang |last4=Wang |first4=Hui |last5=Wang |first5=Xiaolong |title=Association between an indel polymorphism within the distal promoter of EGLN2 and cancer risk: An updated meta-analysis |journal=Molecular Genetics & Genomic Medicine |date=October 2019 |volume=7 |issue=10 |pages=e00936 |doi=10.1002/mgg3.936|pmid=31414584 |pmc=6785434 }}</ref>

== In RNA Polymerase II (RNAP2) ==
Distal promoters in RNA polymerase II bind at enhancer elements and may act as a marker for active regulatory sequences.<ref>{{Cite journal |last1=Savic |first1=Daniel |last2=Roberts |first2=Brian S. |last3=Carleton |first3=Julia B. |last4=Partridge |first4=E. Christopher |last5=White |first5=Michael A. |last6=Cohen |first6=Barak A. |last7=Cooper |first7=Gregory M. |last8=Gertz |first8=Jason |last9=Myers |first9=Richard M. |date=December 2015 |title=Promoter-distal RNA polymerase II binding discriminates active from inactive CCAAT/ enhancer-binding protein beta binding sites |journal=Genome Research |volume=25 |issue=12 |pages=1791–1800 |doi=10.1101/gr.191593.115 |issn=1549-5469 |pmc=4665001 |pmid=26486725}}</ref>

== References ==
{{reflist|30em}}

[[Category:Genetics]]

Distal promoter - История изменений

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