<P> Inhibition of RNA polymerase activity can also be regulated by DNA sequences called silencers . 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 . </P> <P> 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 . 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 . </P> <P> R - loops are formed during transcription . An R - loop is a three - stranded nucleic acid structure containing a DNA - RNA hybrid region and an associated non-template single - stranded DNA . Actively transcribed regions of DNA often form R - loops that are vulnerable to DNA damage . Introns reduce R - loop formation and DNA damage in highly expressed yeast genes . </P> <P> Transcription, a highly regulated phase in gene expression, produces primary transcripts . However, transcription is only the first step which should be followed by many modifications that yield functional forms of RNAs . Otherwise stated, the newly synthesized primary transcripts are modified in several ways to be converted to their mature, functional forms to produce different proteins and RNAs such as mRNA, tRNA, and rRNA . </P>

Primary transcript in the nucleus of a eukaryotic cell