YY1 associates with the macrosatellite DXZ4 on the inactive X chromosome and binds with CTCF to a hypomethylated form in some male carcinomas.
YY1 associates with the macrosatellite DXZ4 on the inactive X chromosome and binds with CTCF to a hypomethylated form in some male carcinomas.
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DOI：
10.1093/nar/gkr964
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发表时间：
2012-02
影响因子：
14.9
通讯作者：
Chadwick BP
中科院分区：
文献类型：
--
作者：
Moseley SC;Rizkallah R;Tremblay DC;Anderson BR;Hurt MM;Chadwick BP
DXZ4是一个X连锁的大卫星，由12-100个3kb重复单位组成。在女性中，它在两个等位基因上采用相反的染色质排列，以响应X染色体的失活。在雄性和活跃的X染色体上，它被包装成异染色质，但在非活跃的X染色体(XI)上，它采用CTCF结合的等色构象。在这里，我们报告了普遍存在的转录因子YY1与DXZ4在XI上的常染色形式相关联。YY1与CTCF的结合使人想起在其他表观遗传调控序列上的结合，包括基因组印迹位点和X-失活中心，这表明这种排列中的一种常见作用模式。与CTCF一样，在体外，CpG甲基化不会阻止YY1与DXZ4的结合，但在体内，这两种蛋白都被限制为低甲基化形式。在几个雄性癌细胞系中，DXZ4在细胞转化反应中可以形成类似XI的构象，其特征是CpG低甲基化和YY1与CTCF的结合。对来自同一个体的男性黑色素瘤细胞系和正常皮肤细胞的分析证实，染色质状态的转变是对转化的反应。
DXZ4 is an X-linked macrosatellite composed of 12–100 tandemly arranged 3-kb repeat units. In females, it adopts opposite chromatin arrangements at the two alleles in response to X-chromosome inactivation. In males and on the active X chromosome, it is packaged into heterochromatin, but on the inactive X chromosome (Xi), it adopts a euchromatic conformation bound by CTCF. Here we report that the ubiquitous transcription factor YY1 associates with the euchromatic form of DXZ4 on the Xi. The binding of YY1 close to CTCF is reminiscent of that at other epigenetically regulated sequences, including sites of genomic imprinting, and at the X-inactivation centre, suggesting a common mode of action in this arrangement. As with CTCF, binding of YY1 to DXZ4 in vitro is not blocked by CpG methylation, yet in vivo both proteins are restricted to the hypomethylated form. In several male carcinoma cell lines, DXZ4 can adopt a Xi-like conformation in response to cellular transformation, characterized by CpG hypomethylation and binding of YY1 and CTCF. Analysis of a male melanoma cell line and normal skin cells from the same individual confirmed that a transition in chromatin state occurred in response to transformation.
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