The Homeobox Gene Mohawk Represses Transcription by Recruiting the Sin3A/HDAC Co-repressor Complex
The Homeobox Gene Mohawk Represses Transcription by Recruiting the Sin3A/HDAC Co-repressor Complex
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DOI：
10.1002/dvdy.21873
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发表时间：
2009-03-01
影响因子：
2.5
通讯作者：
Rawls, Alan
中科院分区：
文献类型：
--
作者：
Anderson, Douglas M.;Beres, Brian J.;Rawls, Alan
Mohawk是一种非典型的同源异型盒基因，在骨骼肌、肌腱和软骨的胚胎祖细胞中表达。我们证明，莫霍克功能作为一个转录抑制因子能够阻断10 T1/2成纤维细胞的肌原性转化。阻遏物活性位于蛋白质羧基末端一半的三个小的进化保守结构域（MRD 1 -3）中。点突变分析表明，MRD 1中的6个残基足以实现阻遏物功能。Mohawk的羧基末端的一半能够募集Sin 3A/HDAC共阻遏物复合物的组分（Sin 3A，Hdac 1和Sap 18）和聚合酶11通用转录因子的子集（Thp，TFIIA 1和TFIIB）。此外，Sap 18，一种将Sin 3A/HDAC复合物与DNA结合的转录因子连接的蛋白质，被MRD 1共免疫沉淀。这些数据预测，莫霍克可以通过招募Sin 3A/HDAC共阻遏物复合物来抑制转录，并因此抑制细胞分化为肌源性谱系所需的靶基因。发展动力学238：572-580，2009年。(C)2009 Wiley-Liss，Inc.
Mohawk is an atypical homeobox gene expressed in embryonic progenitor cells of skeletal muscle, tendon, and cartilage. We demonstrate that Mohawk functions as a transcriptional repressor capable of blocking the myogenic conversion of 10T1/2 fibroblasts. The repressor activity is located in three small, evolutionarily conserved domains (MRD1-3) in the carboxy-terminal half of the protein. Point mutation analysis revealed six residues in MRD1 are sufficient for repressor function. The carboxy-terminal half of Mohawk is able to recruit components of the Sin3A/HDAC co-repressor complex (Sin3A, Hdac1, and Sap18) and a subset of Polymerase 11 general transcription factors (Thp, TFIIA1 and TFIIB). Furthermore, Sap18, a protein that bridges the Sin3A/HDAC complex to DNA-bound transcription factors, is coimmunoprecipitated by MRD1. These data predict that Mohawk can repress transcription through recruitment of the Sin3A/HDAC co-repressor complex, and as a result, repress target genes required for the differentiation of cells to the myogenic lineage. Developmental Dynamics 238:572-580, 2009. (C) 2009 Wiley-Liss, Inc.