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; Yasuyuki Ohkawa

doi:10.1038/s41467-018-03845-1

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, Yasuyuki Ohkawa

Research output: Contribution to journal › Article › peer-review

17 Citations (Scopus)

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.

Original language	English
Article number	1400
Journal	Nature communications
Volume	9
Issue number	1
DOIs	https://doi.org/10.1038/s41467-018-03845-1
Publication status	Published - Dec 1 2018

All Science Journal Classification (ASJC) codes

Chemistry(all)
Biochemistry, Genetics and Molecular Biology(all)
Physics and Astronomy(all)

Access to Document

10.1038/s41467-018-03845-1

Cite this

Harada, A., Maehara, K., Ono, Y., Taguchi, H., Yoshioka, K., Kitajima, Y., Xie, Y., Sato, Y., Iwasaki, T., Nogami, J., Okada, S., Komatsu, T., Semba, Y., Takemoto, T., Kimura, H., Kurumizaka, H., & Ohkawa, Y. (2018). Histone H3.3 sub-variant H3mm7 is required for normal skeletal muscle regeneration. Nature communications, 9(1), [1400]. https://doi.org/10.1038/s41467-018-03845-1

@article{55122f834c264b7c91d6375391b367bc,

title = "Histone H3.3 sub-variant H3mm7 is required for normal skeletal muscle regeneration",

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.",

author = "Akihito Harada and Kazumitsu Maehara and Yusuke Ono and Hiroyuki Taguchi and Kiyoshi Yoshioka and Yasuo Kitajima and Yan Xie and Yuko Sato and Takeshi Iwasaki and Jumpei Nogami and Seiji Okada and Tetsuro Komatsu and Yuichiro Semba and Tatsuya Takemoto and Hiroshi Kimura and Hitoshi Kurumizaka and Yasuyuki Ohkawa",

note = "Funding Information: We thank the Advanced Computational Scientific Program of the Research Institute for Information Technology, Kyushu University and the National Institute of Genetics (NIG) for providing high-performance computing resources. We also thank the Joint Usage and Joint Research Programs, the Institute of Advanced Medical Sciences, Tokushima University and beamline scientists at the Photon Factory for their assistance with data collection from the SPring-8 BL41XU beamline and the BL-1A, BL-5A, and BL-17A beamlines. The synchrotron radiation experiments were performed with approval of the Japan Synchrotron Radiation Research Institute (JASRI) (Proposal 2013A1036 and 2014A1042) and the Photon Factory Program Advisory Committee (Proposal 2012G569, and 2014G556). This work was supported by JST CREST [JPMJCR16G1]; MEXT/JSPS KAKENHI [JP25116010, JP25132709, JP25118518, JP26290064, JP17H03608, and JP17K19356 to Y.O.; JP16H01219 and JP15K18457 to A.H.; JP16K18479, JP16H01577, and JP16H01550 to K.M.; JP25116002 and JP17H01408 to H.Ku.; and JP25116005 to H.Ki.] and is also partially supported by the Platform Project for Supporting Drug Discovery and Life Science Research [to H.Ku.] and the Practical Research Project for Allergic Diseases and Immunology (Research on Allergic Diseases and Immunology) [JP17ek0410044 to Y.Oh.] from the Japan Agency for Medical Research and Development (AMED). H.Ku. was also supported by the Waseda Research Institute for Science and Engineering and by programs of Waseda University. H.T. was supported by a Research Fellowship of the Japan Society for the Promotion of Science for Young Scientists. Publisher Copyright: {\textcopyright} 2018 The Author(s).",

year = "2018",

month = dec,

day = "1",

doi = "10.1038/s41467-018-03845-1",

language = "English",

volume = "9",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

number = "1",

}

TY - JOUR

T1 - Histone H3.3 sub-variant H3mm7 is required for normal skeletal muscle regeneration

AU - Harada, Akihito

AU - Maehara, Kazumitsu

AU - Ono, Yusuke

AU - Taguchi, Hiroyuki

AU - Yoshioka, Kiyoshi

AU - Kitajima, Yasuo

AU - Xie, Yan

AU - Sato, Yuko

AU - Iwasaki, Takeshi

AU - Nogami, Jumpei

AU - Okada, Seiji

AU - Komatsu, Tetsuro

AU - Semba, Yuichiro

AU - Takemoto, Tatsuya

AU - Kimura, Hiroshi

AU - Kurumizaka, Hitoshi

AU - Ohkawa, Yasuyuki

N1 - Funding Information: We thank the Advanced Computational Scientific Program of the Research Institute for Information Technology, Kyushu University and the National Institute of Genetics (NIG) for providing high-performance computing resources. We also thank the Joint Usage and Joint Research Programs, the Institute of Advanced Medical Sciences, Tokushima University and beamline scientists at the Photon Factory for their assistance with data collection from the SPring-8 BL41XU beamline and the BL-1A, BL-5A, and BL-17A beamlines. The synchrotron radiation experiments were performed with approval of the Japan Synchrotron Radiation Research Institute (JASRI) (Proposal 2013A1036 and 2014A1042) and the Photon Factory Program Advisory Committee (Proposal 2012G569, and 2014G556). This work was supported by JST CREST [JPMJCR16G1]; MEXT/JSPS KAKENHI [JP25116010, JP25132709, JP25118518, JP26290064, JP17H03608, and JP17K19356 to Y.O.; JP16H01219 and JP15K18457 to A.H.; JP16K18479, JP16H01577, and JP16H01550 to K.M.; JP25116002 and JP17H01408 to H.Ku.; and JP25116005 to H.Ki.] and is also partially supported by the Platform Project for Supporting Drug Discovery and Life Science Research [to H.Ku.] and the Practical Research Project for Allergic Diseases and Immunology (Research on Allergic Diseases and Immunology) [JP17ek0410044 to Y.Oh.] from the Japan Agency for Medical Research and Development (AMED). H.Ku. was also supported by the Waseda Research Institute for Science and Engineering and by programs of Waseda University. H.T. was supported by a Research Fellowship of the Japan Society for the Promotion of Science for Young Scientists. Publisher Copyright: © 2018 The Author(s).

PY - 2018/12/1

Y1 - 2018/12/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85045261155&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85045261155&partnerID=8YFLogxK

U2 - 10.1038/s41467-018-03845-1

DO - 10.1038/s41467-018-03845-1

M3 - Article

C2 - 29643389

AN - SCOPUS:85045261155

SN - 2041-1723

VL - 9

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 1400

ER -

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

Abstract

All Science Journal Classification (ASJC) codes

Access to Document

Other files and links

Fingerprint

Cite this