TY - JOUR
T1 - Unusual nucleosome formation and transcriptome influence by the histone H3mm18 variant
AU - Hirai, Seiya
AU - Tomimatsu, Kosuke
AU - Miyawaki-Kuwakado, Atsuko
AU - Takizawa, Yoshimasa
AU - Komatsu, Tetsuro
AU - Tachibana, Taro
AU - Fukushima, Yutaro
AU - Takeda, Yasuko
AU - Negishi, Lumi
AU - Kujirai, Tomoya
AU - Koyama, Masako
AU - Ohkawa, Yasuyuki
AU - Kurumizaka, Hitoshi
N1 - Publisher Copyright:
© The Author(s) 2021. Published by Oxford University Press on behalf of Nucleic Acids Research.
PY - 2022/1/11
Y1 - 2022/1/11
N2 - 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.
AB - 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.
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U2 - 10.1093/nar/gkab1137
DO - 10.1093/nar/gkab1137
M3 - Article
C2 - 34929737
AN - SCOPUS:85123651942
SN - 0305-1048
VL - 50
SP - 72
EP - 91
JO - Nucleic Acids Research
JF - Nucleic Acids Research
IS - 1
ER -