Selective and antagonistic functions of SWI/SNF and Mi-2β nucleosome remodeling complexes during an inflammatory response
Selective and antagonistic functions of SWI/SNF and Mi-2β nucleosome remodeling complexes during an inflammatory response
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DOI：
10.1101/gad.1383206
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发表时间：
2006-02-01
影响因子：
10.5
通讯作者：
Smale, ST
中科院分区：
文献类型：
--
作者：
Ramirez-Carrozzi, VR;Nazarian, AA;Smale, ST
对哺乳动物基因在急性刺激下激活的研究表明，染色质结构和核小体重塑事件有助于诱导基因转录的机制多种多样。然而，由于这种多样性，核小体重塑和基因诱导方面的基因组的逻辑组织仍然模糊不清。许多促炎基因在巨噬细胞中响应于微生物感染而被快速诱导。在这里，我们表明，在脂多糖刺激的巨噬细胞，催化BRG 1/BRM亚基的SWI/SNF类ATP依赖性核小体重塑复合物的激活的二级响应基因和诱导的主要响应基因的动力学延迟，但不是快速诱导的主要响应基因。令人惊讶的是，Mi-2 β复合物与SWI/SNF复合物一起沿着被选择性地募集到次级应答和延迟的初级应答基因的控制区，Mi-2 β复合物拮抗性地起作用以限制这些基因类别的诱导。SWI/SNF和Mi-2 β复合物以类似的拮抗方式影响细胞大小。这些结果提供了对核小体重塑复合物对快速诱导确定类别的哺乳动物基因的差异贡献的深入了解，并揭示了Mi-2 β的强大抗炎功能。
Studies of mammalian genes activated in response to an acute stimulus have suggested diverse mechanisms through which chromatin structure and nucleosome remodeling events contribute to inducible gene transcription. However, because of this diversity, the logical organization of the genome with respect to nucleosome remodeling and gene induction has remained obscure. Numerous proinflammatory genes are rapidly induced in macrophages in response to microbial infection. Here, we show that in lipopolysaccharide-stimulated macrophages, the catalytic BRG1/BRM subunits of the SWI/SNF class of ATP-dependent nucleosome remodeling complexes are consistently required for the activation of secondary response genes and primary response genes induced with delayed kinetics, but not for rapidly induced primary response genes. Surprisingly, a Mi-2 beta complex was selectively recruited along with the SWI/SNF complexes to the control regions of secondary response and delayed primary response genes, with the Mi-2 beta complex acting antagonistically to limit the induction of these gene classes. SWI/SNF and Mi-2 beta complexes influenced cell size in a similarly antagonistic manner. These results provide insight into the differential contributions of nucleosome remodeling complexes to the rapid induction of defined classes of mammalian genes and reveal a robust anti-inflammatory function of Mi-2 beta.