Histone acetylation controls the inactive X chromosome replication dynamics
Histone acetylation controls the inactive X chromosome replication dynamics
复制标题
DOI：
10.1038/ncomms1218
复制
发表时间：
2011-03-01
影响因子：
16.6
通讯作者：
Cardoso, M. Cristina
中科院分区：
文献类型：
--
作者：
Casas-Delucchi, Corella S.;Brero, Alessandro;Cardoso, M. Cristina
在哺乳动物中，雄性和雌性细胞之间的剂量补偿是通过灭活一条雌性X染色体(XI)来实现的。有人认为，XI的晚期复制参与了其沉默状态的维持。在这里，我们展示了在S早期到中期的1到2小时内，通过用绿色荧光蛋白标记的复制蛋白在活的哺乳动物细胞中进行DNA复制，XI高度同步复制。XI在核周或核周兼性异染色质之前复制或伴随核周兼性异染色质复制，在构成异染色质之前复制。来自常染色体的X失活特异转录本(Xist)基因的异位表达施加了相同的同步复制模式。我们使用了影响不同表观遗传标记的突变和化学抑制以及可诱导的Xist表达，我们证明了组蛋白低乙酰化在控制xi复制中起着关键作用。XI的表观遗传控制、高度协调的复制让人想起基因组激活前苍蝇和青蛙的胚胎基因组复制，可能是转录沉默染色质的一个共同特征。
In mammals, dosage compensation between male and female cells is achieved by inactivating one female X chromosome (Xi). Late replication of Xi was proposed to be involved in the maintenance of its silenced state. Here, we show a highly synchronous replication of the Xi within 1 to 2 h during early-mid S-phase by following DNA replication in living mammalian cells with green fluorescent protein-tagged replication proteins. The Xi was replicated before or concomitant with perinuclear or perinucleolar facultative heterochromatin and before constitutive heterochromatin. Ectopic expression of the X-inactive-specific transcript (Xist) gene from an autosome imposed the same synchronous replication pattern. We used mutations and chemical inhibition affecting different epigenetic marks as well as inducible Xist expression and we demonstrate that histone hypoacetylation has a key role in controlling Xi replication. The epigenetically controlled, highly coordinated replication of the Xi is reminiscent of embryonic genome replication in flies and frogs before genome activation and might be a common feature of transcriptionally silent chromatin.