Транскрипцияны реттеудегі коактиваторлардың ролі

Class of proteins involved in regulation of transcription

A coactivator is a type of transcriptional coregulator that binds to an activator (a transcription factor) to increase the rate of transcription of a gene or set of genes. The activator contains a DNA binding domain that binds either to a DNA promoter site or a specific DNA regulatory sequence called an enhancer. Binding of the activator coactivator complex increases the speed of transcription by recruiting general transcription machinery to the promoter, therefore increasing gene expression. The use of activators and coactivators allows for highly specific expression of certain genes depending on cell type and developmental stage.

Some coactivators indirectly regulate gene expression by binding to an activator and inducing a conformational change that then allows the activator to bind to the DNA enhancer or promoter sequence. Once the activator coactivator complex binds to the enhancer, RNA polymerase II and other general transcription machinery are recruited to the DNA and transcription begins.

Nuclear DNA is normally wrapped tightly around histones, making it hard or impossible for the transcription machinery to access the DNA. This association is due primarily to the electrostatic attraction between the DNA and histones as the DNA phosphate backbone is negatively charged and histones are rich in lysine residues, which are positively charged. The tight DNA histone association prevents the transcription of DNA into RNA. Many coactivators have histone acetyltransferase (HAT) activity meaning that they can acetylate specific lysine residues on the N terminal tails of histones. In this method, an activator binds to an enhancer site and recruits a HAT complex that then acetylates nucleosomal promoter bound histones by neutralizing the positively charged lysine residues. Acetylation is crucial for synthesis, stability, function, regulation and localization of proteins and RNA transcripts. HAT mediated histone acetylation is reversed using histone deacetylase (HDAC), which catalyzes the hydrolysis of lysine residues, removing the acetyl group from the histones.

Many coactivators also function as corepressors under certain circumstances. The use of activation and coactivation allows for greater control over when, where and how much of a protein is produced.