Histone acetyltransferase
Encyclopedia
Histone acetyltransferases (HAT) are enzyme
s that acetylate
conserved lysine
amino acid
s on histone
proteins by transferring an acetyl group from acetyl CoA
to form ε-N-acetyl lysine.
In general, histone acetylation is linked to transcriptional activation and associated with euchromatin
. When it was first discovered, it was thought that acetylation of lysine neutralizes the positive charge
normally present, thus reducing affinity between histone and (negatively charged) DNA, which renders DNA more accessible to transcription factors. Research has emerged, since, to show that lysine acetylation and other posttranslational modification
s of histones generate binding sites for specific protein–protein interaction domains, such as the acetyl-lysine-binding bromodomain
. Histone acetyltransferases can also acetylate non-histone proteins, such as transcription factors and nuclear receptors to facilitate gene expression.
s (HDACs) are recruited to their target promoters through a physical interaction with a sequence-specific transcription factor (TF). They usually function within a multimolecular complex ('enzymatic complex'), in which the other subunits are necessary for them to modify nucleosomes around the binding site. These enzymes can also modify factors other than histones (protein X).
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
s that acetylate
Acetylation
Acetylation describes a reaction that introduces an acetyl functional group into a chemical compound...
conserved 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....
amino acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...
s 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...
proteins by transferring an acetyl group from acetyl CoA
Coenzyme A
Coenzyme A is a coenzyme, notable for its role in the synthesis and oxidation of fatty acids, and the oxidation of pyruvate in the citric acid cycle. All sequenced genomes encode enzymes that use coenzyme A as a substrate, and around 4% of cellular enzymes use it as a substrate...
to form ε-N-acetyl lysine.
In general, histone acetylation is linked to transcriptional activation and associated with euchromatin
Euchromatin
Euchromatin is a lightly packed form of chromatin that is rich in gene concentration, and is often under active transcription. Unlike heterochromatin, it is found in both cells with nuclei and cells without nuclei...
. When it was first discovered, it was thought that acetylation of lysine neutralizes the positive charge
Electric charge
Electric charge is a physical property of matter that causes it to experience a force when near other electrically charged matter. Electric charge comes in two types, called positive and negative. Two positively charged substances, or objects, experience a mutual repulsive force, as do two...
normally present, thus reducing affinity between histone and (negatively charged) DNA, which renders DNA more accessible to transcription factors. Research has emerged, since, to show that lysine acetylation and other posttranslational modification
Posttranslational modification
Posttranslational modification is the chemical modification of a protein after its translation. It is one of the later steps in protein biosynthesis, and thus gene expression, for many proteins....
s of histones generate binding sites for specific protein–protein interaction domains, such as the acetyl-lysine-binding bromodomain
Bromodomain
A bromodomain is a protein domain that recognizes acetylated lysine residues such as those on the N-terminal tails of histones. This recognition is often a prerequisite for protein-histone association and chromatin remodeling. The domain itself adopts an all-α protein fold, a bundle of four alpha...
. Histone acetyltransferases can also acetylate non-histone proteins, such as transcription factors and nuclear receptors to facilitate gene expression.
Examples
Human proteins that possess histone acetyltransferase catalytic activity include:- CREBBP, CDY1CDY1Testis-specific chromodomain protein Y 1 is a protein that in humans is encoded by the CDY1 gene.-Further reading:...
, CDY2, CDYL1, CLOCKCLOCKClock is a gene encoding a basic-helix-loop-helix-PAS transcription factor that affects both the persistence and period of circadian rhythms... - ELP3ELP3Elongator complex protein 3 is a protein that in humans is encoded by the ELP3 gene.-Further reading:...
, EP300EP300E1A binding protein p300 also known as EP300 or p300 is a protein that, in humans, is encoded by the EP300 gene. This protein regulates the activity of many genes in tissues throughout the body... - HAT1HAT1Histone acetyltransferase 1, also known as HAT1, is an enzyme that, in humans, is encoded by the HAT1 gene.- Function :The protein encoded by this gene is a type B histone acetyltransferase that is involved in the rapid acetylation of newly synthesized cytoplasmic histones, which are, in turn,...
- KAT2A, KAT2BPCAFP300/CBP-associated factor , also known as K acetyltransferase 2B , is a human gene and trancriptional coactivator associated with p53.-Structure:...
, KAT5 - MYST1MYST1Probable histone acetyltransferase MYST1 is an enzyme that in humans is encoded by the MYST1 gene.-Further reading:...
, MYST2MYST2Histone acetyltransferase MYST2 is an enzyme that in humans is encoded by the MYST2 gene.-Interactions:MYST2 has been shown to interact with Androgen receptor, ORC1L and Vimentin.-Further reading:...
, MYST3MYST3MYST histone acetyltransferase 3, also known as MYST3, is an enzyme that, in humans, is encoded by the MYST3 gene.- Function :...
, MYST4MYST4Histone acetyltransferase MYST4 is an enzyme that in humans is encoded by the MYST4 gene.... - NCOA1Nuclear receptor coactivator 1The nuclear receptor coactivator 1 is a transcriptional coregulatory protein that contains several nuclear receptor interacting domains and an intrinsic histone acetyltransferase activity . NCOA1 is recruited to DNA promotion sites by ligand-activated nuclear receptors. NCOA1, in turn, acylates...
, NCOA2Nuclear receptor coactivator 2The nuclear receptor coactivator 2 is a transcriptional coregulatory protein which contains several nuclear receptor interacting domains and an intrinsic histone acetyltransferase activity. NCOA2 is recruited to DNA promotion sites by ligand activated nuclear receptors. NCOA2 in turn acylates...
, NCOA3Nuclear receptor coactivator 3The nuclear receptor coactivator 3 also known as NCOA3 is a protein that, in humans, is encoded by the NCOA3 gene. NCOA3 is also frequently called 'amplified in breast 1' , steroid receptor coactivator-3 , or thyroid hormone receptor activator molecule 1 .-Function:NCOA3 is a transcriptional...
, NCOATMGEA5Bifunctional protein NCOAT is a protein that in humans is encoded by the MGEA5 gene.-Further reading:... - TF3C4GTF3C4General transcription factor 3C polypeptide 4 is a protein that in humans is encoded by the GTF3C4 gene.-Interactions:GTF3C4 has been shown to interact with GTF3C2, GTF3C1, POLR3C and GTF3C5.-Further reading:...
Interaction with HDACs
Histone acetyltransferases (HATs) and histone deacetylaseHistone 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 (HDACs) are recruited to their target promoters through a physical interaction with a sequence-specific transcription factor (TF). They usually function within a multimolecular complex ('enzymatic complex'), in which the other subunits are necessary for them to modify nucleosomes around the binding site. These enzymes can also modify factors other than histones (protein X).
See also
- Histone-Modifying EnzymesHistone-Modifying EnzymesThe packaging of the eukaryotic genome into highly condensed chromatin makes it inaccessible to the factors required for gene transcription, DNA replication, recombination and repair. Eukaryotes have developed intricate mechanisms to overcome this repressive barrier imposed by the chromatin...
- Histone deacetylaseHistone deacetylaseHistone 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...
- Histone methyltransferaseHistone methyltransferaseHistone methyltransferases are enzymes, histone-lysine N-methyltransferase and histone-arginine N-methyltransferase, that catalyze the transfer of one to three methyl groups from the cofactor S-Adenosyl methionine to lysine and arginine residues of histone proteins...
- RNA polymerase control by chromatin structure
- AcetyltransferaseAcetyltransferaseAcetyltransferase is a type of transferase enzyme that transfers an acetyl group.Examples include:* Histone acetyltransferases including CBP histone acetyltransferase* Choline acetyltransferase* Chloramphenicol acetyltransferase...