Oct1 Is a Switchable, Bipotential Stabilizer of Repressed and Inducible Transcriptional States
Oct1 Is a Switchable, Bipotential Stabilizer of Repressed and Inducible Transcriptional States
复制标题
DOI：
10.1074/jbc.m110.174045
复制
发表时间：
2011-01-07
影响因子：
4.8
通讯作者：
Tantin, Dean
中科院分区：
文献类型：
--
作者：
Shakya, Arvind;Kang, Jinsuk;Tantin, Dean
关于 Oct1 转录因子如何调节靶基因表达知之甚少。使用鼠成纤维细胞和两个靶基因 Polr2a 和 Ahcy，我们发现 Oct1 招募 Jmjd1a/KDM3A 赖氨酸脱甲基酶来催化去除抑制性组蛋白 H3K9 二甲基标记并阻断抑制。使用纯化的小鼠 T 细胞和 Il2 靶位点，以及结肠癌细胞系和 Cdx2 靶位点，我们发现 Oct1 募集 NuRD 染色质重塑复合物以促进抑制状态，但以受调控的方式可以切换到不同的能力并介导 Jmjd1a 募集以阻止抑制。这些发现表明，Oct1 通过涉及 NuRD 的机制维持抑制，并通过涉及 Jmjd1a 的抗抑制机制维持平衡的基因表达状态。我们认为，Oct1 不是基因激活或抑制的主要触发因素，而是抑制和诱导状态的可切换稳定剂。
Little is known regarding how the Oct1 transcription factor regulates target gene expression. Using murine fibroblasts and two target genes, Polr2a and Ahcy, we show that Oct1 recruits the Jmjd1a/KDM3A lysine demethylase to catalyze the removal of the inhibitory histone H3K9 dimethyl mark and block repression. Using purified murine T cells and the Il2 target locus, and a colon cancer cell line and the Cdx2 target locus, we show that Oct1 recruits the NuRD chromatin-remodeling complex to promote a repressed state, but in a regulated manner can switch to a different capacity and mediate Jmjd1a recruitment to block repression. These findings indicate that Oct1 maintains repression through a mechanism involving NuRD and maintains poised gene expression states through an antirepression mechanism involving Jmjd1a. We propose that, rather than acting as a primary trigger of gene activation or repression, Oct1 is a switchable stabilizer of repressed and inducible states.