Jae-Hyun Yanga, Yunkyoung Songa, Ja-Hwan Seola, Jin Young Parka, Yong-Jin Yanga, Jeung-Whan Hana, Hong-Duk Younb, and Eun-Jung Choa,1
aSchool of Pharmacy, Sungkyunkwan University, Suwon, Gyeonggi-do 440-746, Republic of Korea; and
bDepartment of Biomedical Sciences, Seoul National University College of Medicine, Seoul 110-799, Republic of Korea
Edited by Steven Henikoff, Fred Hutchinson Cancer Research Center, Seattle, WA, and approved November 5, 2010 (received for review July 13, 2010)
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
myogenesis, histone exchange
1To whom correspondence should be addressed.
Author contributions: J.-H.Y. and E.-J.C. designed research; J.-H.Y., J.-H.S., and J.Y.P. performed research; J.-H.Y., Y.S., J.-H.S., and E.-J.C. analyzed data; Y.S., J.-H.S., Y.-J.Y., J.-W.H., and H.-D.Y. contributed new reagents/analytic tools; and J.-H.Y. and E.-J.C. wrote the paper.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission.
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