Plasma Cell Differentiation is Regulated by the Expression of Histone Variant H3.3

Overview

Journal Nat Commun

Specialty Biology

Date 2024 Jun 20

PMID 38902223

Authors

Yuichi Saito

Akihito Harada

Miho Ushijima

Kaori Tanaka

Ryota Higuchi

Akemi Baba

Daisuke Murakami

Stephen L Nutt

Takashi Nakagawa

Yasuyuki Ohkawa

Yoshihiro Baba

Affiliations

Soon will be listed here.

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.

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