Editing Primary transcript (section)

===Regulation===

A number of factors contribute to the activation and inhibition of transcription and therefore regulate the production of primary transcripts from a given DNA template.{{cn|date=July 2024}}

Activation of RNA polymerase activity to produce primary transcripts is often controlled by sequences of DNA called [[enhancers]]. [[Transcription factors]], proteins that bind to DNA elements to either activate or repress transcription, bind to enhancers and recruit enzymes that alter [[nucleosome]] components, causing DNA to be either more or less accessible to RNA polymerase. The unique combinations of either activating or inhibiting transcription factors that bind to enhancer DNA regions determine whether or not the gene that enhancer interacts with is activated for transcription or not.<ref name="Gilbert2013">{{cite book| vauthors = Gilbert SF |title=Developmental Biology|url=https://books.google.com/books?id=-e_bmgEACAAJ|date=15 July 2013|publisher=Sinauer Associates, Incorporated|isbn=978-1-60535-173-5|pages=38–39, 50}}</ref> Activation of transcription depends on whether or not the transcription elongation complex, itself consisting of a variety of transcription factors, can induce RNA polymerase to dissociate from the [[Mediator (coactivator)|Mediator]] complex that connects an enhancer region to the promoter.<ref name="Gilbert2013" /> [[File:Role of transcription factor in gene expression regulation.svg|thumb|Role of transcription factors and enhancers in gene expression regulation]]

Inhibition of RNA polymerase activity can also be regulated by DNA sequences called [[silencer (DNA)|silencer]]s. Like enhancers, silencers may be located at locations farther up or downstream from the genes they regulate. These DNA sequences bind to factors that contribute to the destabilization of the initiation complex required to activate RNA polymerase, and therefore inhibit transcription.<ref>{{cite book| vauthors = Brown TA | title=Genomes | chapter=Assembly of the Transcription Initiation Complex | date=2002 | edition = 2nd |chapter-url=https://www.ncbi.nlm.nih.gov/books/NBK21115/ | location = Oxford |publisher= Wiley-Liss}}</ref>

[[Histone]] modification by transcription factors is another key regulatory factor for transcription by RNA polymerase. In general, factors that lead to histone [[acetylation]] activate transcription while factors that lead to histone [[deacetylation]] inhibit transcription.<ref name="Lodish2008">{{cite book| vauthors = Lodish H |title=Molecular Cell Biology|url=https://books.google.com/books?id=K3JbjG1JiUMC|year=2008|publisher=W. H. Freeman|isbn=978-0-7167-7601-7|pages=303–306}}</ref> Acetylation of histones induces repulsion between negative components within nucleosomes, allowing for RNA polymerase access. Deacetylation of histones stabilizes tightly coiled nucleosomes, inhibiting RNA polymerase access. In addition to acetylation patterns of histones, methylation patterns at promoter regions of DNA can regulate RNA polymerase access to a given template. RNA polymerase is often incapable of synthesizing a primary transcript if the targeted gene's promoter region contains specific methylated cytosines— residues that hinder binding of transcription-activating factors and recruit other enzymes to stabilize a tightly bound nucleosome structure, excluding access to RNA polymerase and preventing the production of primary transcripts.<ref name="Gilbert2013" />