title: Regulation of histone acetylation and transcription by nuclear protein pp32, a subunit of the INHAT complex.
abstract: Histone acetylation by p300/CBP and PCAF coactivators is considered to be a key mechanism of chromatin modification and transcriptional regulation. A multiprotein cellular complex, INHAT (inhibitor of acetyltransferases), containing the Set/TAF-Ibeta oncoprotein and pp32 strongly inhibits the HAT activity of p300/CBP and PCAF by histone masking. Here we report that the INHAT complex and its subunits have overlapping but distinct HAT inhibitory and histone binding characteristics. We provide evidence suggesting that the histone binding and INHAT activity of pp32 can be regulated by its physical association with other INHAT subunits. In vivo colocalization and transfection studies show that pp32 INHAT domains are responsible for histone binding, HAT inhibitory activity, and repression of transcription. We propose that INHAT and its subunits may function by modulating histone acetyltransferases through a histone-masking mechanism and may play important regulatory roles in the establishment and maintenance of the newly proposed "histone code" of chromatin.
authors.affiliation: Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Sang-beom
authors.initials: SB
authors.lastname: Seo
authors.forename: Todd
authors.initials: T
authors.lastname: Macfarlan
authors.forename: Peter
authors.initials: P
authors.lastname: McNamara
authors.forename: Rui
authors.initials: R
authors.lastname: Hong
authors.forename: Yuki
authors.initials: Y
authors.lastname: Mukai
authors.forename: Soyoung
authors.initials: S
authors.lastname: Heo
authors.forename: Debabrata
authors.initials: D
authors.lastname: Chakravarti
mesh_terms: D016475:3T3 Cells; D000818:Animals; D002843:Chromatin / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D050881:E1A-Associated p300 Protein; D006367:HeLa Cells; D006657:Histones / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008856:Microscopy, Fluorescence; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism*; D010455:Peptides / Q000737:chemistry; D010750:Phosphoproteins / Q000378:metabolism*; D010957:Plasmids / Q000378:metabolism; D011233:Precipitin Tests; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000378:metabolism; D015534:Trans-Activators / Q000737:chemistry / Q000378:metabolism*; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014162:Transfection
chemical_list: D002843:Chromatin; D006657:Histones; D009687:Nuclear Proteins; D010455:Peptides; D010750:Phosphoproteins; D011994:Recombinant Proteins; D015534:Trans-Activators; D050881:E1A-Associated p300 Protein; C494361:Ep300 protein, mouse