Corecruitment of the Grg4 repressor by PU.1 is critical for Pax5-mediated repression of B-cell-specific genes
Corecruitment of the Grg4 repressor by PU.1 is critical for Pax5-mediated repression of B-cell-specific genes
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DOI：
10.1038/sj.embor.7400089
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发表时间：
2004-03-01
期刊：
影响因子：
7.7
通讯作者：
Pettersson, S
中科院分区：
文献类型：
--
作者：
Linderson, Y;Eberhard, D;Pettersson, S
PU.1和Pax 5是B系细胞中免疫球蛋白重链（IgH）基因表达的重要调节因子。我们以前已经表明，PU.1可以增强IgH HS 1，2增强子连接的报告基因的转录，和Pax 5在瞬时转染试验中抑制相同的增强子。在这里，我们报告说，PU.1，像Pax 5，可以招募和物理相互作用的格劳乔家庭的成员，共抑制剂，Grg 4。因此，当募集Grg 4时，PU.1与Pax 5一起以位置依赖性方式抑制增强子功能。有趣的是，Grg 4水平在B细胞活化后降低，表明Grg 4的时间调节。此外，具有类似HS 1，2的活性模式和结构的连接链启动子也可以通过Pax 5/PU.1/Grg 4的组合作用而被抑制。这些数据表明，Pax 5依赖于PU.1，顺式作用，稳定募集Grg共阻遏物的B细胞特异性基因。
PU.1 and Pax5 are important regulators of immunoglobulin heavy-chain (IgH) gene expression in B lineage cells. We have previously shown that PU.1 can potentiate the transcription of an IgH HS1,2 enhancer-linked reporter gene, and that Pax5 represses the same enhancer in transient transfection assays. Here we report that PU.1, like Pax5, can recruit and physically interact with a member of the Groucho family of co-repressors, Grg4. As a consequence, PU.1 in conjunction with Pax5 represses enhancer function in a position-dependent manner when Grg4 is recruited. Interestingly, Grg4 levels decrease following B-cell activation, suggesting temporal regulation of Grg4. Moreover, the joining-chain promoter, with an activity pattern and architecture resembling HS1,2, can also be repressed by the combinatorial action of Pax5/PU.1/Grg4. These data indicate that Pax5 depends on PU.1, acting in cis, for stable recruitment of Grg co-repressors to B-cell-specific genes.