Histone H3.3 sub-variant H3mm7 is required for normal skeletal muscle regeneration

Akihito Harada, Kazumitsu Maehara, Yusuke Ono, Hiroyuki Taguchi, Kiyoshi Yoshioka, Yasuo Kitajima, Yan Xie, Yuko Sato, Takeshi Iwasaki, Jumpei Nogami, Seiji Okada, Tetsuro Komatsu, Yuichiro Semba, Tatsuya Takemoto, Hiroshi Kimura, Hitoshi Kurumizaka and Yasuyuki Ohkawa ()
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Akihito Harada: Kyushu University
Kazumitsu Maehara: Kyushu University
Yusuke Ono: Nagasaki University
Hiroyuki Taguchi: Waseda University
Kiyoshi Yoshioka: Nagasaki University
Yasuo Kitajima: Nagasaki University
Yan Xie: Waseda University
Yuko Sato: Tokyo Institute of Technology
Takeshi Iwasaki: Kyushu University
Jumpei Nogami: Kyushu University
Seiji Okada: Graduate School of Medical Sciences, Kyushu University
Tetsuro Komatsu: Kyushu University
Yuichiro Semba: Kyushu University
Tatsuya Takemoto: Tokushima University
Hiroshi Kimura: Tokyo Institute of Technology
Hitoshi Kurumizaka: Waseda University
Yasuyuki Ohkawa: Kyushu University

Nature Communications, 2018, vol. 9, issue 1, 1-13

Abstract: Abstract Regulation of gene expression requires selective incorporation of histone H3 variant H3.3 into chromatin. Histone H3.3 has several subsidiary variants but their functions are unclear. Here we characterize the function of histone H3.3 sub-variant, H3mm7, which is expressed in skeletal muscle satellite cells. H3mm7 knockout mice demonstrate an essential role of H3mm7 in skeletal muscle regeneration. Chromatin analysis reveals that H3mm7 facilitates transcription by forming an open chromatin structure around promoter regions including those of myogenic genes. The crystal structure of the nucleosome containing H3mm7 reveals that, unlike the S57 residue of other H3 proteins, the H3mm7-specific A57 residue cannot form a hydrogen bond with the R40 residue of the cognate H4 molecule. Consequently, the H3mm7 nucleosome is unstable in vitro and exhibited higher mobility in vivo compared with the H3.3 nucleosome. We conclude that the unstable H3mm7 nucleosome may be required for proper skeletal muscle differentiation.

Date: 2018
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-03845-1

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DOI: 10.1038/s41467-018-03845-1

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