BRWD1 gene expression is repressed by STAT5

Based on a mouse model study of pro-B cells, binding of Signal transducer and activator of transcription 5A and 5B (STAT5A or STAT5B), activated in response to Interleukin-7 (IL7) signaling to the BRWD1 gene promoter, results in the inhibition of Bromodomain and WD repeat-containing protein 1 (BRWD1) transcription. STAT5 binding coincides with the appearance of H3K27me3 marks at the BRWD1 promoter, a marker of repressed chromatin (Mandal et al. 2015). STAT5 is able to recruit the polycomb repressive complex (PRC2) to genes silenced in response to IL7 signaling (Mandal et al. 2011), which may explain the H3K27me3 marks at STAT5-bound BRWD1 promoter.<p>In pre-B cells, in contrast to pro-B cells, IL7 signaling is downregulated, which induces BRWD1 transcription. BRWD1 enhances the recruitment of the recombinase complex V(D)J recombination-activating protein 1: V(D)J recombination-activating protein 2 (RAG1:RAG2) to the immunoglobulin kappa locus, thus promoting V(D)J recombination - a key event in B lymphopoiesis (Mandal et al. 2015).

基于对B细胞前体细胞的啮齿动物模型研究，STAT5A或STAT5B转录因子在响应白介素-7（IL7）信号至BRWD1基因启动子时被激活，其与BRWD1启动子的结合导致Bromodomain和WD重复结构域蛋白1（BRWD1）转录的抑制。STAT5的结合与BRWD1启动子处的H3K27me3标记的出现相一致，H3K27me3标记是抑制性染色质的标志（Mandal等人，2015年）。STAT5能够招募多梳抑制复合物（PRC2）至IL7信号响应中沉默的基因，这或许可以解释STAT5结合的BRWD1启动子处的H3K27me3标记（Mandal等人，2011年）。在B细胞前体细胞中，与B细胞前体细胞相反，IL7信号被下调，这诱导了BRWD1的转录。BRWD1增强了重组酶复合物V(D)J重组激活蛋白1：V(D)J重组激活蛋白2（RAG1:RAG2）至免疫球蛋白κ位点的募集，从而促进V(D)J重组——这是B细胞发生过程中的一个关键事件（Mandal等人，2015年）。