Institut Curie, PSL Research University, CNRS UMR3215, INSERM U934, UPMC Paris-Sorbonne, 26 Rue d'Ulm, 75005, Paris, France.
Department of Physiology, Development and Neuroscience, Wellcome Trust Cancer Research UK Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QN, UK.
Nat Commun. 2017 Nov 3;8(1):1297. doi: 10.1038/s41467-017-01415-5.
X-chromosome inactivation is established during early development. In mice, transcriptional repression of the paternal X-chromosome (Xp) and enrichment in epigenetic marks such as H3K27me3 is achieved by the early blastocyst stage. X-chromosome inactivation is then reversed in the inner cell mass. The mechanisms underlying Xp reactivation remain enigmatic. Using in vivo single-cell approaches (allele-specific RNAseq, nascent RNA-fluorescent in situ hybridization and immunofluorescence), we show here that different genes are reactivated at different stages, with more slowly reactivated genes tending to be enriched in H3meK27. We further show that in UTX H3K27 histone demethylase mutant embryos, these genes are even more slowly reactivated, suggesting that these genes carry an epigenetic memory that may be actively lost. On the other hand, expression of rapidly reactivated genes may be driven by transcription factors. Thus, some X-linked genes have minimal epigenetic memory in the inner cell mass, whereas others may require active erasure of chromatin marks.
X 染色体失活是在早期发育过程中建立的。在小鼠中，通过早期囊胚阶段实现了父本 X 染色体 (Xp) 的转录抑制和表观遗传标记（如 H3K27me3）的富集。然后，X 染色体失活在内部细胞团中被逆转。Xp 重新激活的机制仍然是个谜。使用体内单细胞方法（等位基因特异性 RNAseq、新生 RNA-荧光原位杂交和免疫荧光），我们在这里表明，不同的基因在不同的阶段被重新激活，重新激活较慢的基因往往富集 H3meK27。我们进一步表明，在 UTX H3K27 组蛋白去甲基酶突变体胚胎中，这些基因的重新激活更加缓慢，这表明这些基因携带的表观遗传记忆可能被主动丢失。另一方面，快速重新激活的基因的表达可能由转录因子驱动。因此，一些 X 连锁基因在内部细胞团中几乎没有表观遗传记忆，而其他基因可能需要主动擦除染色质标记。
