Transient transcription in the early embryo sets an epigenetic state that programs postnatal growth
Transient transcription in the early embryo sets an epigenetic state that programs postnatal growth
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DOI：
10.1038/ng.3718
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发表时间：
2017-01-01
期刊：
影响因子：
30.8
通讯作者：
Bourc'his, Deborah
中科院分区：
文献类型：
--
作者：
Greenberg, Maxim V. C.;Glaser, Juliane;Bourc'his, Deborah
早期胚胎事件编程影响成人生理的表观遗传状态的可能性仍然是健康和发育中的一个重要问题。使用印记的Zdbf2基因座作为早期表型编程的范例，我们在这里证明了在多能胚胎中发生的染色质变化对于胚胎发育可能是必要的，但相反地在成人中发出重要的调节信息。LIZ转录本在早期胚胎和胚胎干细胞(ESCs)中瞬时表达。这种转录局部促进了Zdbf2启动子上游的从头DNA甲基化，从而拮抗了Polycomb介导的Zdbf2的抑制。值得注意的是，缺乏LIZ的小鼠胚胎发育正常，但未能激活出生后大脑中的ZDBF2，并表现出不可磨灭的生长抑制，这意味着LIZ依赖的表观遗传开关起着至关重要的作用。这项工作提供了证据，证明在早期胚胎时间框架内的转录可以编程稳定的表观遗传状态，并在以后产生生理后果。
The potential for early embryonic events to program epigenetic states that influence adult physiology remains an important question in health and development. Using the imprinted Zdbf2 locus as a paradigm for the early programming of phenotypes, we demonstrate here that chromatin changes that occur in the pluripotent embryo can be dispensable for embryogenesis but instead signal essential regulatory information in the adult. The Liz (long isoform of Zdbf2) transcript is transiently expressed in early embryos and embryonic stem cells (ESCs). This transcription locally promotes de novo DNA methylation upstream of the Zdbf2 promoter, which antagonizes Polycomb-mediated repression of Zdbf2. Strikingly, mouse embryos deficient for Liz develop normally but fail to activate Zdbf2 in the postnatal brain and show indelible growth reduction, implying a crucial role for a Liz dependent epigenetic switch. This work provides evidence that transcription during an early embryonic timeframe can program a stable epigenetic state with later physiological consequences.