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===Promoters and regulatory elements=== {{Main|Promoter (genetics)}} Promoters are DNA segments near the 5' end of the gene where transcription begins. They are the sites where [[RNA polymerase]] binds to initiate RNA synthesis. Every gene has a noncoding promoter. [[Cis-regulatory element|Regulatory elements]] are sites that control the [[Transcription (genetics)|transcription]] of a nearby gene. They are almost always sequences where [[transcription factor]]s bind to DNA and these transcription factors can either activate transcription (activators) or repress transcription (repressors). Regulatory elements were discovered in the 1960s and their general characteristics were worked out in the 1970s by studying specific transcription factors in bacteria and [[bacteriophage]].{{citation needed|date=June 2022}} Promoters and regulatory sequences represent an abundant class of noncoding DNA but they mostly consist of a collection of relatively short sequences so they do not take up a very large fraction of the genome. The exact amount of regulatory DNA in mammalian genome is unclear because it is difficult to distinguish between spurious transcription factor binding sites and those that are functional. The binding characteristics of typical [[DNA-binding protein]]s were characterized in the 1970s and the biochemical properties of transcription factors predict that in cells with large genomes, the majority of binding sites will not be biologically functional.{{citation needed|date=June 2022}} Many regulatory sequences occur near promoters, usually upstream of the transcription start site of the gene. Some occur within a gene and a few are located downstream of the transcription termination site. In eukaryotes, there are some regulatory sequences that are located at a considerable distance from the promoter region. These distant regulatory sequences are often called [[Enhancer (genetics)|enhancers]] but there is no rigorous definition of enhancer that distinguishes it from other transcription factor binding sites.<ref>{{cite journal | vauthors = Compe E, Egly JM | title = The Long Road to Understanding RNAPII Transcription Initiation and Related Syndromes | journal = Annual Review of Biochemistry | volume = 90 | pages = 193β219 | date = 2021 | doi = 10.1146/annurev-biochem-090220-112253| pmid = 34153211 | s2cid = 235595550 }}</ref><ref>{{cite journal | vauthors = Visel A, Rubin EM, Pennacchio LA | title = Genomic views of distant-acting enhancers | journal = Nature | volume = 461 | issue = 7261 | pages = 199β205 | date = September 2009 | pmid = 19741700 | pmc = 2923221 | doi = 10.1038/nature08451 | author-link3 = Len A. Pennacchio | bibcode = 2009Natur.461..199V }}</ref>
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