A role for MeCP2 in switching gene activity via chromatin unfolding and HP1γ displacement.
A role for MeCP2 in switching gene activity via chromatin unfolding and HP1γ displacement.
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DOI：
10.1371/journal.pone.0069347
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Verschure PJ
中科院分区：
文献类型：
--
作者：
Brink MC;Piebes DG;de Groote ML;Luijsterburg MS;Casas-Delucchi CS;van Driel R;Rots MG;Cardoso MC;Verschure PJ
甲基cpg结合蛋白2 （MeCP2）通常被认为是一种转录抑制因子，而最近的研究表明MeCP2也参与转录激活。为了深入了解MeCP2的双重功能，我们利用哺乳动物细胞系统中含有乳糖操作符和含有报告基因的染色体结构域，评估了MeCP2对活细胞中高阶染色质结构的影响，以评估乳糖抑制因子标记的MeCP2（和单独的MeCP2结构域）在活细胞中的结合效果。我们的数据显示，MeCP2的靶向结合引发了广泛的染色质展开。mecp2诱导的染色质展开是独立于甲基胞嘧啶结合域触发的。有趣的是，MeCP2结合引发了HP1γ在染色体结构域的丢失和HP1γ流动性的增加，而这在HP1α和HP1β中没有观察到。令人惊讶的是，mecp2诱导的染色质展开与转录激活无关。我们的研究表明MeCP2在重组染色质以促进基因活性转换中的新作用。
Methyl-CpG-binding protein 2 (MeCP2) is generally considered to act as a transcriptional repressor, whereas recent studies suggest that MeCP2 is also involved in transcription activation. To gain insight into this dual function of MeCP2, we assessed the impact of MeCP2 on higher-order chromatin structure in living cells using mammalian cell systems harbouring a lactose operator and reporter gene-containing chromosomal domain to assess the effect of lactose repressor-tagged MeCP2 (and separate MeCP2 domains) binding in living cells. Our data reveal that targeted binding of MeCP2 elicits extensive chromatin unfolding. MeCP2-induced chromatin unfolding is triggered independently of the methyl-cytosine-binding domain. Interestingly, MeCP2 binding triggers the loss of HP1γ at the chromosomal domain and an increased HP1γ mobility, which is not observed for HP1α and HP1β. Surprisingly, MeCP2-induced chromatin unfolding is not associated with transcriptional activation. Our study suggests a novel role for MeCP2 in reorganizing chromatin to facilitate a switch in gene activity.
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