title: Myogenic transcriptional activation of MyoD mediated by replication-independent histone deposition.
abstract: In mammals, the canonical histone H3 and the variant H3.3 are assembled into chromatin through replication-coupled and replication-independent (RI) histone deposition pathways, respectively, to play distinct roles in chromatin function. H3.3 is largely associated with transcriptionally active regions via the activity of RI histone chaperone, HIRA. However, the precise role of the RI pathway and HIRA in active transcription and the mechanisms by which H3.3 affects gene activity are not known. In this study, we show that HIRA is an essential factor for muscle development by establishing MyoD activation in myotubes. HIRA and Asf1a, but not CHD1 or Asf1b, mediate H3.3 incorporation in the promoter and the critical upstream regulatory regions of the MyoD gene. HIRA and H3.3 are required for epigenetic transition into the more permissive chromatin structure for polymerase II recruitment to the promoter, regardless of transcription-associated covalent modification of histones. Our results suggest distinct epigenetic management of the master regulator with RI pathway components for cellular differentiation.
authors.affiliation: School of Pharmacy, Sungkyunkwan University, Suwon, Gyeonggi-do 440-746, Republic of Korea.
authors.forename: Jae-Hyun
authors.initials: JH
authors.lastname: Yang
authors.forename: Yunkyoung
authors.initials: Y
authors.lastname: Song
authors.forename: Ja-Hwan
authors.initials: JH
authors.lastname: Seol
authors.forename: Jin Young
authors.initials: JY
authors.lastname: Park
authors.forename: Yong-Jin
authors.initials: YJ
authors.lastname: Yang
authors.forename: Jeung-Whan
authors.initials: JW
authors.lastname: Han
authors.forename: Hong-Duk
authors.initials: HD
authors.lastname: Youn
authors.forename: Eun-Jung
authors.initials: EJ
authors.lastname: Cho
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002460:Cell Line; D042002:Chromatin Assembly and Disassembly / Q000502:physiology*; D047369:Chromatin Immunoprecipitation; D017931:DNA Primers / Q000235:genetics; D005455:Fluorescent Antibody Technique; D056488:Histone Chaperones / Q000378:metabolism*; D006657:Histones / Q000378:metabolism*; D015151:Immunoblotting; D047468:Immunoprecipitation; D051379:Mice; D046228:Microarray Analysis; D024510:Muscle Development / Q000502:physiology*; D017570:MyoD Protein / Q000378:metabolism*; D034622:RNA Interference; D012342:RNA, Small Nuclear / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000378:metabolism*; D015533:Transcriptional Activation / Q000235:genetics / Q000502:physiology*; D014162:Transfection
chemical_list: D018797:Cell Cycle Proteins; D017931:DNA Primers; C484187:Hira protein, mouse; D056488:Histone Chaperones; D006657:Histones; D017570:MyoD Protein; D012342:RNA, Small Nuclear; D014157:Transcription Factors