Probing p300/CBP Associated Factor (PCAF)-Dependent Pathways with a Small Molecule Inhibitor

PCAF
(KAT2B) belongs to the GNAT family of lysine acetyltransferases
(KAT) and specifically acetylates the histone H3K9 residue and several
nonhistone proteins. PCAF is also a transcriptional coactivator. Due
to the lack of a PCAF KAT-specific small molecule inhibitor, the exclusive
role of the acetyltransferase activity of PCAF is not well understood.
Here, we report that a natural compound of the hydroxybenzoquinone
class, embelin, specifically inhibits H3Lys9 acetylation in mice and
inhibits recombinant PCAF-mediated acetylation with near complete
specificity in vitro. Furthermore, using embelin,
we have identified the gene networks that are regulated by PCAF during
muscle differentiation, further highlighting the broader regulatory
functions of PCAF in muscle differentiation in addition to the regulation
via MyoD acetylation.