10.8: Co-activators and Co-repressors
Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into co-activators or co-repressors based on their function.
An individual co-regulator can function either as a co-activator or a co-repressor, depending on its role in its associated complex. For example, the transcriptional co-repressor G9a participates in the activation of gene expression for a steroid hormone receptor along with other co-activators, such as GRIP1 and CARM1. Distinct domains of the protein perform these varied functions. In addition to the role in the complex, these regulators have enzymatic activities that can help regulate gene expression through the remodeling of the chromatin structure.
Histone acetyltransferases and histone demethylases function as co-activators; however, they first need to be localized to the regulatory site by a transcription activator to be able to perform these functions. Histone acetyltransferases can acetylate the lysine residues on the histone tails. Acetylation uncoils the chromatin and promotes gene expression. On the other hand, histone deacetylases and histone methyltransferases function as co-repressors. Both these modifications lead to the tightening up of chromatin structure and thereby lead to the prevention of gene expression.