Regulation of histone acetylation and transcription by nuclear protein pp32, a subunit of the INHAT complex.
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.
Seo
Sang-beom
SB
Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
Macfarlan
Todd
T
McNamara
Peter
P
Hong
Rui
R
Mukai
Yuki
Y
Heo
Soyoung
S
Chakravarti
Debabrata
D
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
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