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

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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 languageEnglish
Article number1400
JournalNature communications
Volume9
Issue number1
DOIs
Publication statusPublished - Dec 1 2018

All Science Journal Classification (ASJC) codes

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

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    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