Cohesion establishment factor, Eco1 represses transcription via association with histone demethylase, LSD1
Cohesion establishment factor, Eco1 represses transcription via association with histone demethylase, LSD1
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DOI：
10.1016/j.bbrc.2010.03.125
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发表时间：
2010-04-16
影响因子：
3.1
通讯作者：
Kim, Seong-Tae
中科院分区：
文献类型：
--
作者：
Choi, Hyun-Kyung;Kim, Beom-Jun;Kim, Seong-Tae
在细胞分裂过程中，精确的染色体分离需要两个姐妹染色单体从DNA复制到有丝分裂的物理附着，这一过程被称为姐妹染色单体内聚。姐妹染色单体的内聚是由一个四亚基内聚蛋白复合物介导的，它通过分子环将姐妹染色单体连接起来。Ecol是建立姐妹染色单体内聚所必需的乙酰转移酶。Eco1分别在S期和DNA损伤时乙酰化Smc3和Mcd1 （Rad21）以建立内聚。在这里，我们发现Ecol以剂量依赖的方式抑制转录。锌指结构域和乙酰转移酶结构域的突变对Ecol的转录抑制活性没有显著影响。我们观察到组蛋白去甲基化酶Lsd1与Eco1相互作用，并且是Ecol转录抑制活性所必需的。染色质免疫沉淀（ChIP）实验表明，Ecol促进组蛋白H3赖氨酸4的去甲基化。综上所述，我们提供了Eco1通过与组蛋白去甲基酶LSD1相互作用将染色质转化为非活性状态来抑制转录的第一个证据。(C) 2010爱思唯尔公司版权所有。
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. Ecol 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 Ecol repress transcription in a dose-dependent manner. Mutations of zinc-finger domain or acetyltransferase domain did not significantly affect the transcriptional repression activity of Ecol. We observed that histone demethylase, Lsd1 interacts with Eco1 and is required for the transcriptional repression activity of Ecol. Chromatin immunoprecipitation (ChIP) experiments show that Ecol 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. (C) 2010 Elsevier Inc. All rights reserved.