title: pp32, an INHAT component, is a transcription machinery recruiter for maximal induction of IFN-stimulated genes.
abstract: Type I interferon (IFN) plays a crucial role in establishing the cellular antiviral state by inducing transcription of IFN-stimulated genes (ISGs). Generally, histone acetyltransferases (HATs) are positive regulators of transcription, but histone deacetylase (HDAC) activity is essential for transcriptional induction of ISGs. pp32 is known to be a key component of the inhibitor of acetyltransferase (INHAT) complex that inhibits HAT-dependent transcriptional activation. Here, we show that pp32 is involved in the positive regulation of ISG transcription. pp32 interacted with signal transducer and activator of transcription 1 (STAT1) and STAT2 in an IFN-dependent manner. pp32 was not required for tyrosine phosphorylation and nuclear translocation of STATs, but was needed for binding of transcriptional complexes with ISG promoters and, thereby, for maximal transcription activation. pp32 was found to be associated with ISG promoters in IFN-untreated cells, and its binding amount fluctuated as a function of time after IFN treatment. short interfering RNA (siRNA)-mediated knockdown of pp32 expression reduced the histone acetylation level on ISG promoters, suggesting that pp32 plays a role in ISG transcription by a function other than that of INHAT. Taking these findings together, we propose that pp32 is involved in the formation of ISG transcription initiation complexes, possibly as their recruiter.
authors.affiliation: Department of Infection Biology, Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8575, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Kadota
authors.forename: Kyosuke
authors.initials: K
authors.lastname: Nagata
mesh_terms: D000123:Acetyltransferases / Q000037:antagonists & inhibitors*; D002460:Cell Line; D004791:Enzyme Inhibitors / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D016899:Interferon-beta / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins; D011485:Protein Binding; D016601:RNA-Binding Proteins; D050794:STAT1 Transcription Factor / Q000235:genetics / Q000378:metabolism; D050795:STAT2 Transcription Factor / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: C087425:ANP32A protein, human; D004791:Enzyme Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D016601:RNA-Binding Proteins; D050794:STAT1 Transcription Factor; D050795:STAT2 Transcription Factor; D016899:Interferon-beta; D000123:Acetyltransferases