A POP-1 repressor complex restricts inappropriate cell type-specific gene transcription during Caenorhabditis elegans embryogenesis
A POP-1 repressor complex restricts inappropriate cell type-specific gene transcription during Caenorhabditis elegans embryogenesis
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DOI：
10.1093/emboj/20.24.7197
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发表时间：
2001-12-17
期刊：
影响因子：
11.4
通讯作者：
Shi, Y
中科院分区：
文献类型：
--
作者：
Calvo, D;Victor, M;Shi, Y
在秀丽隐杆线虫中，组蛋白乙酰转移酶 CBP-1 抵消组蛋白脱乙酰酶 HDA-1 的抑制活性，从而允许内胚层分化，这是由 E 细胞指定的。在姐妹 MS 细胞中，内胚层的命运通过一种未知的机制被含有 HMG 盒的蛋白质 POP-1 的作用所阻止。在这项研究中，我们发现 CBP-1、HDA-1 和 POP-1 汇聚在 end-1（一种初始内胚层决定基因）上。在 E 谱系中，CBP-1 的一个重要功能似乎是激活 end-1 转录。通过证明 POP-1 作为转录抑制因子抑制不适当的 end-1 转录，我们进一步确定了 POP-1 在 MS 谱系中抑制内胚层作用的分子机制。我们提供的证据表明，POP-1 通过招募 HDA-1 和 UNC-37（共抑制子 Groucho 的线虫同源物）来抑制转录。这些发现证明了乙酰转移酶和脱乙酰酶之间的相互作用在发育过程中关键细胞命运决定基因的调节中的重要性。此外，他们还确定了一种策略，通过该策略，历史上的脱乙酰酶和其他共阻遏物的协同作用可确保最大程度地抑制不适当的细胞类型特异性基因转录。
In Caenorhabditis elegans, histone acetyltransferase CBP-1 counteracts the repressive activity of the histone deacetylase HDA-1 to allow endoderm differentiation, which is specified by the E cell. In the sister MS cell, the endoderm fate is prevented by the action of an HMG box-containing protein, POP-1, through an unknown mechanism. In this study, we show that CBP-1, HDA-1 and POP-1 converge on end-1, an initial endoderm-determining gene. In the E lineage, an essential function of CBP-1 appears to be the activation of end-1 transcription. We further identify a molecular mechanism for the endoderm-suppressive effect of POP-1 in the MS lineage by demonstrating that POP-1 functions as a transcriptional repressor that inhibits inappropriate end-1 transcription. We provide evidence that POP-1 represses transcription via the recruitment of HDA-1 and UNC-37, the C.elegans homolog of the co-repressor Groucho. These findings demonstrate the importance of the interplay between acetyltransferases and deacetylases in the regulation of a critical cell fate-determining gene during development. Furthermore, they identify a strategy by which concerted actions of historic deacetylases and other co-repressors ensure maximal repression of inappropriate cell type-specific gene transcription.