木村計画研究代表、胡桃坂計画研究代表、山縣計画研究分担による成果が Journal of Cell Biology 誌に掲載されました!

ISWI chromatin remodeling complexes recruit NSD2 and H3K36me2 in pericentromeric heterochromatin

Naoki Goto, Kazuma Suke, Nao Yonezawa, Hidenori Nishihara, Tetsuya Handa, Yuko Sato, Tomoya Kujirai, Hitoshi Kurumizaka, Kazuo Yamagata, Hiroshi Kimura

Abstract
Histone H3 lysine36 dimethylation (H3K36me2) is generally distributed in the gene body and euchromatic intergenic regions. However, we found that H3K36me2 is enriched in pericentromeric heterochromatin in some mouse cell lines. We here revealed the mechanism of heterochromatin targeting of H3K36me2. Among several H3K36 methyltransferases, NSD2 was responsible for inducing heterochromatic H3K36me2. Depletion and overexpression analyses of NSD2-associating proteins revealed that NSD2 recruitment to heterochromatin was mediated through the imitation switch (ISWI) chromatin remodeling complexes, such as BAZ1B-SMARCA5 (WICH), which directly binds to AT-rich DNA via a BAZ1B domain-containing AT-hook-like motifs. The abundance and stoichiometry of NSD2, SMARCA5, and BAZ1B could determine the localization of H3K36me2 in different cell types. In mouse embryos, H3K36me2 heterochromatin localization was observed at the two- to four-cell stages, suggesting its physiological relevance.

J Cell Biol. 223(8):e202310084. doi: 10.1083/jcb.202310084.
PMID: 38709169 DOI: 10.1083/jcb.202310084
https://rupress.org/jcb/article/223/8/e202310084/276730/ISWI-chromatin-remodeling-complexes-recruit-NSD2