title: Silencing of IFN-stimulated gene transcription is regulated by histone H1 and its chaperone TAF-I.
abstract: Chromatin structure and its alteration play critical roles in the regulation of transcription. However, the transcriptional silencing mechanism with regard to the chromatin structure at an unstimulated state of the interferon (IFN)-stimulated gene (ISG) remains unclear. Here we investigated the role of template activating factor-I (TAF-I, also known as SET) in ISG transcription. Knockdown (KD) of TAF-I increased ISG transcript and simultaneously reduced the histone H1 level on the ISG promoters during the early stages of transcription after IFN stimulation from the unstimulated state. The transcription factor levels on the ISG promoters were increased in TAF-I KD cells only during the early stages of transcription. Furthermore, histone H1 KD also increased ISG transcript. TAF-I and histone H1 double KD did not show the additive effect in ISG transcription, suggesting that TAF-I and histone H1 may act on the same regulatory pathway to control ISG transcription. In addition, TAF-I KD and histone H1 KD affected the chromatin structure near the ISG promoters. On the basis of these findings, we propose that TAF-I and its target histone H1 are key regulators of the chromatin structure at the ISG promoter to maintain the silent state of ISG transcription.
authors.affiliation: Department of Infection Biology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8575, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Kadota
authors.affiliation: Department of Infection Biology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8575, Japan knagata@md.tsukuba.ac.jp.
authors.forename: Kyosuke
authors.initials: K
authors.lastname: Nagata
mesh_terms: D002843:Chromatin / Q000737:chemistry; D004268:DNA-Binding Proteins; D020868:Gene Silencing; D057809:HEK293 Cells; D006367:HeLa Cells; D056488:Histone Chaperones / Q000378:metabolism* / Q000502:physiology; D006657:Histones / Q000378:metabolism*; D006801:Humans; D016899:Interferon-beta / Q000494:pharmacology*; D011401:Promoter Regions, Genetic; D020218:Response Elements; D050791:STAT Transcription Factors / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism* / Q000502:physiology; D015533:Transcriptional Activation
chemical_list: D002843:Chromatin; D004268:DNA-Binding Proteins; D056488:Histone Chaperones; D006657:Histones; C513473:SET protein, human; D050791:STAT Transcription Factors; D014157:Transcription Factors; D016899:Interferon-beta