Coactivator (genetics)
Encyclopedia
A coactivator is a protein that increases gene expression
by binding to an activator
(or transcription factor
) which contains a DNA binding domain
. The coactivator is unable to bind DNA by itself.
The coactivator can enhance transcription initiation by stabilizing the formation of the RNA polymerase
holoenzyme enabling faster clearance of the promoter. Coactivators may control many other substeps of transcription, including elongation, RNA splicing, and termination and degradation of the coactivator-activator complex.
Some coactivators possess intrinsic histone acetyltransferase
(HAT) activity, which acetylates histone
s and causes chromatin
to relax in a limited region allowing increased access to the DNA
. CBP and p300 are examples of coactivators with HAT activity. Numerous other enzyme activities have been reported among the 300 known coactivators for nuclear receptors. The most well known of these are SRC-1, SRC-2, and SRC-3. Coactivators work in high molecular weight complexes of 6-10 coactivator and coactivator-associated proteins (termed co-coactivators).
The same coactivator will likely be used to increase transcription of many different genes, since it is the activator that provides the specificity to a particular sequence. Recent evidence indicates that coactivators may have diverse roles outside of transcription and that they may act as 'master genes' for regulating major cellular and metabolic growth processes.
In humans several dozen to several hundred coactivators are known, depending on the level of confidence with which the characterisation of a protein as a coactivator can be made.
Gene expression
Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product. These products are often proteins, but in non-protein coding genes such as ribosomal RNA , transfer RNA or small nuclear RNA genes, the product is a functional RNA...
by binding to an activator
Activator (genetics)
An activator is a DNA-binding protein that regulates one or more genes by increasing the rate of transcription. The activator may increase transcription by virtue of a connected domain which assists in the formation of the RNA polymerase holoenzyme, or may operate through a coactivator. A...
(or transcription factor
Transcription factor
In molecular biology and genetics, a transcription factor is a protein that binds to specific DNA sequences, thereby controlling the flow of genetic information from DNA to mRNA...
) which contains a DNA binding domain
DNA-binding protein
DNA-binding proteins are proteins that are composed of DNA-binding domains and thus have a specific or general affinity for either single or double stranded DNA. Sequence-specific DNA-binding proteins generally interact with the major groove of B-DNA, because it exposes more functional groups that...
. The coactivator is unable to bind DNA by itself.
The coactivator can enhance transcription initiation by stabilizing the formation of the RNA polymerase
RNA polymerase
RNA polymerase is an enzyme that produces RNA. In cells, RNAP is needed for constructing RNA chains from DNA genes as templates, a process called transcription. RNA polymerase enzymes are essential to life and are found in all organisms and many viruses...
holoenzyme enabling faster clearance of the promoter. Coactivators may control many other substeps of transcription, including elongation, RNA splicing, and termination and degradation of the coactivator-activator complex.
Some coactivators possess intrinsic histone acetyltransferase
Histone acetyltransferase
Histone acetyltransferases are enzymes that acetylate conserved lysine amino acids on histone proteins by transferring an acetyl group from acetyl CoA to form ε-N-acetyl lysine....
(HAT) activity, which acetylates histone
Histone
In biology, histones are highly alkaline proteins found in eukaryotic cell nuclei that package and order the DNA into structural units called nucleosomes. They are the chief protein components of chromatin, acting as spools around which DNA winds, and play a role in gene regulation...
s and causes chromatin
Chromatin
Chromatin is the combination of DNA and proteins that make up the contents of the nucleus of a cell. The primary functions of chromatin are; to package DNA into a smaller volume to fit in the cell, to strengthen the DNA to allow mitosis and meiosis and prevent DNA damage, and to control gene...
to relax in a limited region allowing increased access to the DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
. CBP and p300 are examples of coactivators with HAT activity. Numerous other enzyme activities have been reported among the 300 known coactivators for nuclear receptors. The most well known of these are SRC-1, SRC-2, and SRC-3. Coactivators work in high molecular weight complexes of 6-10 coactivator and coactivator-associated proteins (termed co-coactivators).
The same coactivator will likely be used to increase transcription of many different genes, since it is the activator that provides the specificity to a particular sequence. Recent evidence indicates that coactivators may have diverse roles outside of transcription and that they may act as 'master genes' for regulating major cellular and metabolic growth processes.
In humans several dozen to several hundred coactivators are known, depending on the level of confidence with which the characterisation of a protein as a coactivator can be made.
External links
- Nuclear Receptor Signalling Atlas (NIH-funded research consortium and database; includes open-access PubMed-indexed journal, Nuclear Receptor Signaling)