Bop encodes a muscle-restricted protein containing MYND and SET domains and is essential for cardiac differentiation and morphogenesis
Bop encodes a muscle-restricted protein containing MYND and SET domains and is essential for cardiac differentiation and morphogenesis
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DOI：
10.1038/ng866
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发表时间：
2002-05-01
期刊：
影响因子：
30.8
通讯作者：
Srivastava, D
中科院分区：
文献类型：
--
作者：
Gottlieb, PD;Pierce, SA;Srivastava, D
许多转录因子在心脏分化过程中调节特定的时空事件;然而，调节这些事件的机制在很大程度上是未知的。使用改良的消减杂交方法，以确定特定的基因，影响早期心脏发育，我们发现，Bop是专门表达的心脏和骨骼肌前体细胞分化之前，这些谱系。Bop编码含有MYND和SET结构域的蛋白质，其已被证明通过介导不同的染色质修饰来调节转录。我们表明，m-Bop是一个组蛋白脱乙酰酶依赖的转录抑制因子。在小鼠中靶向缺失Bop破坏了心室心肌细胞的成熟并干扰了右心室的形成。Hand 2是一种对右心室发育至关重要的转录因子，在心肌细胞前体中的正常表达依赖于m-Bop。这些结果表明，m-Bop是心肌细胞分化和心脏形态发生所必需的。
Many transcription factors regulate specific temporal-spatial events during cardiac differentiation; however, the mechanisms that regulate such events are largely unknown. Using a modified subtractive hybridization method to identify specific genes that influence early cardiac development, we found that Bop is expressed specifically in cardiac and skeletal muscle precursors before differentiation of these lineages. Bop encodes a protein containing MYND and SET domains, which have been shown to regulate transcription by mediating distinct chromatin modifications. We show that m-Bop is a histone deacetylase-dependent transcriptional repressor. Targeted deletion of Bop in mice disrupted maturation of ventricular cardiomyocytes and interfered with formation of the right ventricle. Normal expression of Hand2, a transcription factor essential for right ventricular development, in cardiomyocyte precursors is dependent upon m-Bop. These results indicate that m-Bop is essential for cardiomyocyte differentiation and cardiac morphogenesis.