The HATs are a disparate group of enzymes that can be divided into different families based on their structural homology. The three main families are GNAT (Gcn5-related N-acetyltransferases),MYST (MOZ, YBF2/SAS3, SAS2 and TIP60) and p300/CBP (CREB binding protein).
The HAT of our interest, KAT8, is a member of the MYST family.
This enzyme was originally discovered in Drosophila,where it is involved in dose-compensation of the X-chromosome
gene transcription in male flies.
KAT8 functions in two protein complexes, MSL and MSL1v1, that are conserved throughout the eukaryotic kingdom, including humans.
Both KAT8 complexes have been described to be responsible for acetylating lysine 16 on histone H4 (H4K16) and were shown to play a role in cell cycle progression.
However, only the MSL1v1 complex seems to be involved in acetylation of the tumor suppressor protein p53.
KAT8 has also been shown to play a role in embryonic stem cell renewal.
Embryonic stem cells lacking KAT8 lose differentiation potential and show changes in morphology and gene expression of
essential transcription factors.
Thus, it is clear that KAT8 plays a very important role in normal physiology and disease.