Histone Lysine acetyltransferases
The acetylation of histones is mediated by Lysine acetyltrasferases (KATs). They catalyse the transfer of acetyl group from acetyl-CoA to the e-amino group of specific lysine residues. This neutralises the positive charge of the lysines and hence the histone-DNA interaction is reduced. They can be cytoplasmic and nuclear. Some have the ability to acetylate free as well as nucleosomal histones. We found 19 unique proteins reported in humans that demonstrate the histone acetyltransferases activity. They can be broadly categorised into the following classes:
GCN5 family: e.g. KAT2a, KAT2b,
MYST (SAS/MOZ) family: e.g. MYST1, Kat5, MYST2, MYST3, MYST4,
SRC/p160 nuclear receptor coactivator family: e.g. NCOA1, NCOA3,
P300/CBP family: e.g. p300, CBP.
Lysine acetyltransferases are majorly involved in transcriptional activation. KAT2A and KAT5 have a significant role in DNA damage response. Many of these enzymes have non-histone targets like p53. Myst1 and PCAF are also important for unperturbed cell cycle progression. SRC1/3 functions under the influence of nuclear hormone mediated signalling and hence are altered in many cancers. Histone lysine acetyltransferases are implicated in Rubinstein-Taybi Syndrome (RTS), familial dysautonomia, colorectal cancers, breast cancers and gastric cancers.
Cytogenetic map of Lysine acetyltransferases coding genes