title: Probing p300/CBP associated factor (PCAF)-dependent pathways with a small molecule inhibitor.
abstract: 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.
authors.affiliation: Transcription and Disease Laboratory, Molecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research , Bangalore, India 560064.
authors.forename: Rahul
authors.initials: R
authors.lastname: Modak
authors.forename: Jeelan
authors.initials: J
authors.lastname: Basha
authors.forename: Narendra
authors.initials: N
authors.lastname: Bharathy
authors.forename: Koustav
authors.initials: K
authors.lastname: Maity
authors.forename: Pushpak
authors.initials: P
authors.lastname: Mizar
authors.forename: Akshay V
authors.initials: AV
authors.lastname: Bhat
authors.forename: Madavan
authors.initials: M
authors.lastname: Vasudevan
authors.forename: Vinay Kumar
authors.initials: VK
authors.lastname: Rao
authors.forename: Wai Kay
authors.initials: WK
authors.lastname: Kok
authors.forename: Nagashayana
authors.initials: N
authors.lastname: Natesh
authors.forename: Reshma
authors.initials: R
authors.lastname: Taneja
authors.forename: Tapas K
authors.initials: TK
authors.lastname: Kundu
mesh_terms: D000107:Acetylation / Q000187:drug effects*; D000818:Animals; D016227:Benzoquinones / Q000737:chemistry / Q000494:pharmacology*; D002454:Cell Differentiation; D002460:Cell Line; D005786:Gene Expression Regulation / Q000187:drug effects; D057809:HEK293 Cells; D006657:Histones / Q000378:metabolism; D006801:Humans; D051379:Mice; D017570:MyoD Protein / Q000378:metabolism; D032446:Myoblasts / Q000166:cytology / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D050880:p300-CBP Transcription Factors / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D000099224:p300-CBP-Associated Factor
chemical_list: D016227:Benzoquinones; D006657:Histones; D017570:MyoD Protein; D011994:Recombinant Proteins; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor; C010945:embelin