Heard E, Rougeulle C, Arnaud D, Avner P, Allis C D, Spector D L
Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
Cell. 2001 Dec 14;107(6):727-38. doi: 10.1016/s0092-8674(01)00598-0.
Coating of the X chromosome by Xist RNA is an essential trigger for X inactivation. However, little is known about the early chromatin remodeling events that transform this signal into transcriptional silencing. Here we report that methylation of histone H3 lysine 9 on the inactive X chromosome occurs immediately after Xist RNA coating and before transcriptional inactivation of X-linked genes. X-chromosomal H3 Lys-9 methylation occurs during the same window of time as H3 Lys-9 hypoacetylation and H3 Lys-4 hypomethylation. Histone H3 modifications thus represent the earliest known chromatin changes during X inactivation. We also identify a unique "hotspot" of H3 Lys-9 methylation 5' to Xist, and we propose that this acts as a nucleation center for Xist RNA-dependent spread of inactivation along the X chromosome via H3 Lys-9 methylation.
Xist RNA对X染色体的覆盖是X染色体失活的关键触发因素。然而，对于将这一信号转化为转录沉默的早期染色质重塑事件，我们却知之甚少。在此，我们报告，失活X染色体上组蛋白H3赖氨酸9的甲基化在Xist RNA覆盖后即刻发生，且早于X连锁基因的转录失活。X染色体上H3赖氨酸9的甲基化与H3赖氨酸9的低乙酰化以及H3赖氨酸4的低甲基化发生在同一时间段内。因此，组蛋白H3修饰代表了X染色体失活过程中已知最早的染色质变化。我们还在Xist基因5'端鉴定出一个独特的H3赖氨酸9甲基化“热点”，并提出它作为一个成核中心，通过H3赖氨酸9甲基化介导Xist RNA依赖性的失活沿着X染色体传播。
