Committee on Immunology, The University of Chicago, Chicago, IL 60657.
Department of Biochemistry and Molecular Genetics, Northwestern University Feinberg School of Medicine, Chicago, IL 60611.
J Immunol. 2020 Apr 1;204(7):1760-1769. doi: 10.4049/jimmunol.1901188. Epub 2020 Feb 24.
Lymphocyte lineage specification and commitment requires the activation of lineage-specific genes and repression of alternative lineage genes, respectively. The mechanisms governing alternative lineage gene repression and commitment in lymphocytes are largely unknown. In this study, we demonstrate that Ezh2, which represses gene expression through methylation of histone 3 lysine 27, was essential for repression of numerous genes, including genes encoding innate lymphocyte transcription factors, specifically in murine B lymphocyte progenitors, but these cells maintained their B lymphocyte identity. However, adult Ezh2-deficient B lymphocytes expressed , which encodes an RNA-binding protein associated with fetal hematopoietic gene expression programs, and these cells acquired a fetal B-1 lymphocyte phenotype in vitro and in vivo. Therefore, Ezh2 coordinates the repression of multiple gene programs in B lymphocytes and maintains the adult B-2 cell fate.
淋巴细胞谱系的特化和定型分别需要激活谱系特异性基因和抑制其他谱系基因。然而，淋巴细胞中调控替代谱系基因抑制和定型的机制在很大程度上仍是未知的。在这项研究中，我们证明了 Ezh2 通过组蛋白 H3 赖氨酸 27 的甲基化来抑制基因表达，它对于包括先天淋巴细胞转录因子编码基因在内的众多基因的抑制是必不可少的，特别是在小鼠 B 淋巴细胞祖细胞中，但这些细胞仍保持其 B 淋巴细胞特性。然而，成年 Ezh2 缺陷型 B 淋巴细胞表达 Blimp1，它编码一种与胎儿造血基因表达程序相关的 RNA 结合蛋白，这些细胞在体外和体内获得了胎儿 B-1 淋巴细胞表型。因此，Ezh2 协调 B 淋巴细胞中多个基因程序的抑制，并维持成年 B-2 细胞命运。
