The SWI/SNF chromatin remodeling complex regulates germinal center formation by repressing Blimp-1 expression

被引:25
|
作者
Choi, Jinwook
Jeon, Shin
Choi, Seungjin
Park, Kyungsoo
Seong, Rho Hyun [1 ]
机构
[1] Seoul Natl Univ, Sch Biol Sci, Seoul 151742, South Korea
基金
新加坡国家研究基金会;
关键词
SWI/SNF chromatin remodeling complex; follicular helper T cell; germinal center reaction; Blimp-1; T-CELL HOMEOSTASIS; TRANSCRIPTIONAL REPRESSION; B-CELLS; GENE; DIFFERENTIATION; BRG1; INTERACTS; EZH2; PLURIPOTENCY; METHYLATION;
D O I
10.1073/pnas.1418592112
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Germinal center (GC) reaction is crucial in adaptive immune responses. The formation of GC is coordinated by the expression of specific genes including Blimp-1 and Bcl-6. Although gene expression is critically influenced by the status of chromatin structure, little is known about the role of chromatin remodeling factors for regulation of GC formation. Here, we show that the SWI/SNF chromatin remodeling complex is required for GC reactions. Mice lacking Srg3/mBaf155, a core component of the SWI/SNF complex, showed impaired differentiation of GC B and follicular helper T cells in response to T cell-dependent antigen challenge. The SWI/SNF complex regulates chromatin structure at the Blimp-1 locus and represses its expression by interacting cooperatively with Bcl-6 and corepressors. The defect in GC reactions in mice lacking Srg3 was due to the derepression of Blimp-1 as supported by genetic studies with Blimp-1-ablated mice. Hence, our study identifies the SWI/SNF complex as a key mediator in GC reactions by modulating Bcl-6-dependent Blimp-1 repression.
引用
收藏
页码:E718 / E727
页数:10
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