Unusual nucleosome formation and transcriptome influence by the histone H3mm18 variant

Seiya Hirai, Kosuke Tomimatsu, Atsuko Miyawaki-Kuwakado, Yoshimasa Takizawa, Tetsuro Komatsu, Taro Tachibana, Yutaro Fukushima, Yasuko Takeda, Lumi Negishi, Tomoya Kujirai, Masako Koyama, Yasuyuki Ohkawa, Hitoshi Kurumizaka

    Research output: Contribution to journalArticlepeer-review

    2 Citations (Scopus)

    Abstract

    Histone H3mm18 is a non-allelic H3 variant expressed in skeletal muscle and brain in mice. However, its function has remained enigmatic. We found that H3mm18 is incorporated into chromatin in cells with low efficiency, as compared to H3.3. We determined the structures of the nucleosome core particle (NCP) containing H3mm18 by cryo-electron microscopy, which revealed that the entry/exit DNA regions are drastically disordered in the H3mm18 NCP. Consistently, the H3mm18 NCP is substantially unstable in vitro. The forced expression of H3mm18 in mouse myoblast C2C12 cells markedly suppressed muscle differentiation. A transcriptome analysis revealed that the forced expression of H3mm18 affected the expression of multiple genes, and suppressed a group of genes involved in muscle development. These results suggest a novel gene expression regulation system in which the chromatin landscape is altered by the formation of unusual nucleosomes with a histone variant, H3mm18, and provide important insight into understanding transcription regulation by chromatin.

    Original languageEnglish
    Pages (from-to)72-91
    Number of pages20
    JournalNucleic acids research
    Volume50
    Issue number1
    DOIs
    Publication statusPublished - Jan 11 2022

    All Science Journal Classification (ASJC) codes

    • Genetics

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