Histone Acetyltransferases

Histone Acetyltransferases (HATs; also known as Lysine Aceyltransferases or KATs) are catalytic domains found in a diverse range of proteins; there are 37 endogenous mammalian proteins that are thought to have HAT activity. HAT domains can be found in proteins alongside other epigenetic domains, such as bromodomains, which recognize acetylated lysine residues. Proteins with HAT activity are found in multiprotein complexes, the components of which regulate HAT specificity and integration with other proteins, as well as enabling the detection of post-translational modifications.

HATs are grouped into families based on their amino acid sequence homology:

• MYST family, including MOZ (also known as KAT6A or MYST3), Tip60 (KAT5), HBO1 (KAT7) and MOF (KAT8)
• p300/CBP family, including CBP (CREB-binding protein; KAT3A) and p300 (KAT3B)
• GNAT family, including GCN5 (KAT2A) and PCAF (KAT2B)

Function of HATs

The function of HATs is to catalyze the acetylation of lysine residues in proteins, by the transfer of an acetyl group from acetyl CoA to form ε-N-acetyl lysine. The reverse process, removal of acetylation marks, is catalyzed by histone deacetylases (HDACs; also known as lysine deacetylases or KDACs). Over 2000 actylation targets have been identified including proteins from most subcellular compartments and organelles. Acetylation of lysine residues can affect the cellular localization and catalytic activity of a protein, as well as its ability to interact with other proteins. This post-translation modification governs the ability of proteins to respond to intracellular and extracellular processes.

HATs act on gene regulatory elements of transcriptionally-active genes, such as promoter and enhancer regions, to modulate transcriptional output. For example, MOF and GNC5 localize to promoter regions of their targets, and their identification correlates with increased transcriptional activity. Similarly, p300 and CBP activate transcription via their recruitment by transcription factors, to enhancer and promoter regions. p53 recruits p300 and CBP to its target loci in response to DNA damage, where they mediate the acetylation of histone 3 lysine 18 (H3K18) and H3K27, stimulating RNA polymerase II to leave the promotor and activate transcriptional elongation.

Acetylation of Histones

A key function of HATs is the acetylation of lysine residues on histone protein tails, which is an important epigenetic regulator of chromatin architecture and gene transcription. Acetylation of histone lysine residues, such as H4K16ac, can disrupt interactions between neighbouring nucleosomes, and between histones and DNA. These changes create an environment that is more conducive to transcription. Some histone acetylation marks are also associated with increased release of RNA polymerase, while other acetylation marks affect the recruitment of bromodomain containing proteins.

External sources of pharmacological information for Histone Acetyltransferases :

• BJP Guide

Literature for Histone Acetyltransferases

Tocris offers the following scientific literature for Histone Acetyltransferases to showcase our products. We invite you to request* your copy today!

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Epigenetics Scientific Review

Written by Susanne Müller-Knapp and Peter J. Brown, this review gives an overview of the development of chemical probes for epigenetic targets, as well as the impact of these tool compounds being made available to the scientific community. In addition, their biological effects are also discussed. Epigenetic compounds available from Tocris are listed.

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Histone Acetyltransferase Gene Data