Identification of a Ctcf cofactor, Yy1, for the X chromosome binary switch
Identification of a Ctcf cofactor, Yy1, for the X chromosome binary switch
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DOI：
10.1016/j.molcel.2006.11.017
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发表时间：
2007-01-12
期刊：
影响因子：
16
通讯作者：
Lee, Jeannie T.
中科院分区：
文献类型：
--
作者：
Donohoe, Mary E.;Zhang, Li-Feng;Lee, Jeannie T.
在哺乳动物中，雌性中一条X染色体的失活使XX雌性和XY雄性之间的基因剂量相等。两个非编码基因座，Tsix和Xite，共同调节X染色体的命运，通过控制同源染色体配对，计数，和互斥的选择。在选择之后，Xite和Tsix表达的不对称性驱动了不同的染色体命运，但目前尚不清楚这种模式是如何建立的。虽然没有被证实的反式作用因子已被确定，一个可能的候选人是Ctcf，一个染色质绝缘体与常染色体印迹的基本功能。在这里，我们搜索反式因子，并确定YY 1作为Ctcf所需的辅因子。成对的Ctcf-yy 1元件高度聚集在Tsix的计数/选择和印记域中。YY 1的缺乏导致Tsix和Xist表达异常，导致雄性和雌性胚胎的缺陷。YY 1和Ctcf通过特异性蛋白质-蛋白质相互作用结合，并一起反式激活Tsix。我们建议，Ctcf-YY 1-Tsix复杂的功能作为一个关键组成部分的X染色体的二进制开关。
In mammals, inactivation of one X chromosome in the female equalizes gene dosages between XX females and XY males. Two noncoding loci, Tsix and Xite, together regulate X chromosome fate by controlling homologous chromosome pairing, counting, and mutually exclusive choice. Following choice, the asymmetry of Xite and Tsix expression drives divergent chromosome fates, but how this pattern becomes established is currently unknown. Although no proven trans-acting factors have been identified, a likely candidate is Ctcf, a chromatin insulator with essential function in autosomal imprinting. Here, we search for trans-factors and identify Yy1 as a required cofactor for Ctcf. Paired Ctcf-Yy1 elements are highly clustered within the counting/choice and imprinting domain of Tsix. A deficiency of Yy1 leads to aberrant Tsix and Xist expression, resulting in a deficit of male and female embryos. Yy1 and Ctcf associate through specific protein-protein interactions and together transactivate Tsix. We propose that the Ctcf-Yy1-Tsix complex functions as a key component of the X chromosome binary switch.