Corepressor (genetics)
Encyclopedia
In molecular genetics
, a corepressor is a substance that inhibits the expression
of gene
s. A corepressor downregulates
(or represses) the expression of genes not through direct interaction with a gene promoter (a sequence of DNA
adjacent to the regulated gene), but rather indirectly through interaction with repressor protein
s that in turn bind to the promoter.
In prokaryote
s, the term corepressor is used to denote the activating ligand
of a repressor
protein. For example, the E. coli
tryptophan repressor
(TrpR) is only able to bind to DNA and repress transcription of the Trp operon
when its corepressor tryptophan
is bound to it. TrpR in the absence of tryptophan is known as an aporepressor and is inactive in repressing gene transcription. Trp operon encodes enzymes responsible for the synthesis of tryptophan. Hence TrpR provides a negative feedback
mechanism that regulates the biosynthesis
of tryptophan.
In eukaryote
s, a corepressor is a protein that binds to transcription factor
s. In the absence of corepressors and in the presence of coactivators, transcription factors upregulate gene expression. Coactivators and corepressors compete for the same binding sites on transcription factors. Hence corepressors prevent binding of coactivators to transcription factors which causes a decrease in gene transcription. A second mechanism by which corepressors may repress transcriptional initiation when bound to transcription factor/DNA complexes is by recruiting histone deacetylase
s which catalyze
the removal of acetyl
groups from lysine
residues. This increases the positive charge on histone
s which strengthens the electrostatic
attraction between the positively charged histones and negatively charged DNA, making the DNA less accessible for transcription.
In humans several dozen to several hundred corepressors are known, depending on the level of confidence with which the characterisation of a protein as a corepressors can be made.
Molecular genetics
Molecular genetics is the field of biology and genetics that studies the structure and function of genes at a molecular level. The field studies how the genes are transferred from generation to generation. Molecular genetics employs the methods of genetics and molecular biology...
, a corepressor is a substance that inhibits the expression
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...
of gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
s. A corepressor downregulates
Downregulation and upregulation
Downregulation is the process by which a cell decreases the quantity of a cellular component, such as RNA or protein, in response to an external variable...
(or represses) the expression of genes not through direct interaction with a gene promoter (a sequence of 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...
adjacent to the regulated gene), but rather indirectly through interaction with repressor protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
s that in turn bind to the promoter.
In prokaryote
Prokaryote
The prokaryotes are a group of organisms that lack a cell nucleus , or any other membrane-bound organelles. The organisms that have a cell nucleus are called eukaryotes. Most prokaryotes are unicellular, but a few such as myxobacteria have multicellular stages in their life cycles...
s, the term corepressor is used to denote the activating ligand
Ligand (biochemistry)
In biochemistry and pharmacology, a ligand is a substance that forms a complex with a biomolecule to serve a biological purpose. In a narrower sense, it is a signal triggering molecule, binding to a site on a target protein.The binding occurs by intermolecular forces, such as ionic bonds, hydrogen...
of a repressor
Repressor
In molecular genetics, a repressor is a DNA-binding protein that regulates the expression of one or more genes by binding to the operator and blocking the attachment of RNA polymerase to the promoter, thus preventing transcription of the genes. This blocking of expression is called...
protein. For example, the E. coli
Escherichia coli
Escherichia coli is a Gram-negative, rod-shaped bacterium that is commonly found in the lower intestine of warm-blooded organisms . Most E. coli strains are harmless, but some serotypes can cause serious food poisoning in humans, and are occasionally responsible for product recalls...
tryptophan repressor
Tryptophan repressor
Tryptophan repressor is a transcription factor involved in controlling amino acid metabolism. It has been best studied in Escherichia coli, where it is a dimeric protein that regulates transcription of the 5 genes in the tryptophan operon...
(TrpR) is only able to bind to DNA and repress transcription of the Trp operon
Trp operon
Trp operon is an operon - a group of genes that are used, or transcribed, together - that codes for the components for production of tryptophan. The Trp operon is present in many bacteria, but was first characterized in Escherichia coli. It is regulated so that when tryptophan is present in the...
when its corepressor tryptophan
Tryptophan
Tryptophan is one of the 20 standard amino acids, as well as an essential amino acid in the human diet. It is encoded in the standard genetic code as the codon UGG...
is bound to it. TrpR in the absence of tryptophan is known as an aporepressor and is inactive in repressing gene transcription. Trp operon encodes enzymes responsible for the synthesis of tryptophan. Hence TrpR provides a negative feedback
Negative feedback
Negative feedback occurs when the output of a system acts to oppose changes to the input of the system, with the result that the changes are attenuated. If the overall feedback of the system is negative, then the system will tend to be stable.- Overview :...
mechanism that regulates the biosynthesis
Biosynthesis
Biosynthesis is an enzyme-catalyzed process in cells of living organisms by which substrates are converted to more complex products. The biosynthesis process often consists of several enzymatic steps in which the product of one step is used as substrate in the following step...
of tryptophan.
In eukaryote
Eukaryote
A eukaryote is an organism whose cells contain complex structures enclosed within membranes. Eukaryotes may more formally be referred to as the taxon Eukarya or Eukaryota. The defining membrane-bound structure that sets eukaryotic cells apart from prokaryotic cells is the nucleus, or nuclear...
s, a corepressor is a protein that binds to 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...
s. In the absence of corepressors and in the presence of coactivators, transcription factors upregulate gene expression. Coactivators and corepressors compete for the same binding sites on transcription factors. Hence corepressors prevent binding of coactivators to transcription factors which causes a decrease in gene transcription. A second mechanism by which corepressors may repress transcriptional initiation when bound to transcription factor/DNA complexes is by recruiting histone deacetylase
Histone deacetylase
Histone deacetylases are a class of enzymes that remove acetyl groups from an ε-N-acetyl lysine amino acid on a histone. This is important because DNA is wrapped around histones, and DNA expression is regulated by acetylation and de-acetylation. Its action is opposite to that of histone...
s which catalyze
Catalysis
Catalysis is the change in rate of a chemical reaction due to the participation of a substance called a catalyst. Unlike other reagents that participate in the chemical reaction, a catalyst is not consumed by the reaction itself. A catalyst may participate in multiple chemical transformations....
the removal of acetyl
Acetyl
In organic chemistry, acetyl is a functional group, the acyl with chemical formula COCH3. It is sometimes represented by the symbol Ac . The acetyl group contains a methyl group single-bonded to a carbonyl...
groups from lysine
Lysine
Lysine is an α-amino acid with the chemical formula HO2CCH4NH2. It is an essential amino acid, which means that the human body cannot synthesize it. Its codons are AAA and AAG....
residues. This increases the positive charge on 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 which strengthens the electrostatic
Electrostatics
Electrostatics is the branch of physics that deals with the phenomena and properties of stationary or slow-moving electric charges....
attraction between the positively charged histones and negatively charged DNA, making the DNA less accessible for transcription.
In humans several dozen to several hundred corepressors are known, depending on the level of confidence with which the characterisation of a protein as a corepressors can be made.