Plasma cell differentiation is regulated by the expression of histone variant H3.3

Saito, Y; Harada, A; Ushijima, M; Tanaka, K; Higuchi, R; Baba, A; Murakami, D; Nutt, SL; NAKAGAWA, T; Ohkawa, Y; Baba, Y

Author(s): Saito, Y; Harada, A; Ushijima, M; Tanaka, K; Higuchi, R; Baba, A; Murakami, D; Nutt, SL; NAKAGAWA, T; Ohkawa, Y; Baba, Y;
Details: Publication Year 2024-06-20,Volume 15,Issue #1,Page 5004
Journal Title: Nature Communications
Publication Type: Jun 20 epub ahead of print
Abstract: The differentiation of B cells into plasma cells is associated with substantial transcriptional and epigenetic remodeling. H3.3 histone variant marks active chromatin via replication-independent nucleosome assembly. However, its role in plasma cell development remains elusive. Herein, we show that during plasma cell differentiation, H3.3 is downregulated, and the deposition of H3.3 and chromatin accessibility are dynamically changed. Blockade of H3.3 downregulation by enforced H3.3 expression impairs plasma cell differentiation in an H3.3-specific sequence-dependent manner. Mechanistically, enforced H3.3 expression inhibits the upregulation of plasma cell-associated genes such as Irf4, Prdm1, and Xbp1 and maintains the expression of B cell-associated genes, Pax5, Bach2, and Bcl6. Concomitantly, sustained H3.3 expression prevents the structure of chromatin accessibility characteristic for plasma cells. Our findings suggest that appropriate H3.3 expression and deposition control plasma cell differentiation.
Publisher: Springer Nature
Keywords: *Cell Differentiation/genetics; *Histones/metabolism; *Plasma Cells/metabolism/cytology; Animals; Mice; Chromatin/metabolism/genetics; Humans; Mice, Inbred C57BL; Interferon Regulatory Factors/metabolism/genetics; B-Lymphocytes/metabolism/cytology; Gene Expression Regulation
Research Division(s): Immunology
PubMed ID: 38902223
Publisher's Version: https://doi.org/10.1038/s41467-024-49375-x
Open Access at Publisher's Site: https://doi.org/10.1038/s41467-024-49375-x
Terms of Use/Rights Notice: Refer to copyright notice on published article.
Documents: s41467-024-49375-x.pdf - (3.07MB, application/pdf)

Creation Date: 2024-06-28 10:39:10

Last Modified: 2024-06-28 10:42:43