Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon 440-746, Republic of Korea.
Biochem Biophys Res Commun. 2010 Apr 16;394(4):1063-8. doi: 10.1016/j.bbrc.2010.03.125. Epub 2010 Mar 21.
Accurate chromosome segregation during cell division requires physical attachment of two sister chromatids from DNA replication until mitosis, a process known as sister chromatid cohesion. Sister chromatid cohesion is mediated by a four-subunit cohesin complex that connects sister chromatids by encircling them as molecular rings. Eco1 is an essential acetyltransferase required for the establishment of sister chromatid cohesion. Eco1 acetylates Smc3 and Mcd1 (Rad21) to establish cohesion during S phase and in response to DNA damage, respectively. Here, we show that Eco1 repress transcription in a dose-dependent manner. Mutations of zinc-finger domain or acetyltransferase domain did not significantly affect the transcriptional repression activity of Eco1. We observed that histone demethylase, Lsd1 interacts with Eco1 and is required for the transcriptional repression activity of Eco1. Chromatin immunoprecipitation (ChIP) experiments show that Eco1 facilitates the demethylation of lysine 4 of histone H3. Taken together, we provide the first evidence that Eco1 represses transcription by interacting with histone demethylase, LSD1 to convert chromatin to inactive state.
在细胞分裂过程中，准确的染色体分离需要在 DNA 复制到有丝分裂期间将两条姐妹染色单体物理连接起来，这个过程称为姐妹染色单体黏合。姐妹染色单体黏合由一个由四个亚基组成的黏合复合物介导，该复合物通过环绕姐妹染色单体形成分子环来连接它们。Eco1 是建立姐妹染色单体黏合所必需的一种必需乙酰转移酶。Eco1 乙酰化 Smc3 和 Mcd1（Rad21），分别在 S 期和响应 DNA 损伤时建立黏合。在这里，我们表明 Eco1 以剂量依赖的方式抑制转录。锌指结构域或乙酰转移酶结构域的突变并没有显著影响 Eco1 的转录抑制活性。我们观察到组蛋白去甲基酶 LSD1 与 Eco1 相互作用，并且是 Eco1 转录抑制活性所必需的。染色质免疫沉淀（ChIP）实验表明，Eco1 有助于组蛋白 H3 赖氨酸 4 的去甲基化。总之，我们提供了第一个证据，表明 Eco1 通过与组蛋白去甲基酶 LSD1 相互作用来抑制转录，从而将染色质转化为非活性状态。
