Department of Cell Biology, Emory University, Atlanta, GA 30322, USA.
Department of Cell Biology, Emory University, Atlanta, GA 30322, USA.
Trends Genet. 2020 Mar;36(3):160-176. doi: 10.1016/j.tig.2019.12.004. Epub 2020 Jan 29.
Like breadcrumbs in the forest, cotranscriptionally acquired histone methylation acts as a memory of prior transcription. Because it can be retained through cell divisions, transcriptional memory allows cells to coordinate complex transcriptional programs during development. However, if not reprogrammed properly during cell fate transitions, it can also disrupt cellular identity. In this review, we discuss the consequences of failure to reprogram histone methylation during three crucial epigenetic reprogramming windows: maternal reprogramming at fertilization, embryonic stem cell (ESC) differentiation, and the continuous maintenance of cell identity in differentiated cells. In addition, we discuss how following the wrong breadcrumb trail of transcriptional memory provides a framework for understanding how heterozygous loss-of-function mutations in histone-modifying enzymes may cause severe neurodevelopmental disorders.
如同森林中的面包屑一样，共转录获得的组蛋白甲基化可作为先前转录的记忆。由于它可以通过细胞分裂保留下来，转录记忆使细胞能够在发育过程中协调复杂的转录程序。然而，如果在细胞命运转变过程中没有正确地重新编程，它也可能破坏细胞的身份。在这篇综述中，我们讨论了在三个关键的表观遗传重编程窗口中未能重新编程组蛋白甲基化的后果：受精时的母体重编程、胚胎干细胞 (ESC) 分化以及分化细胞中细胞身份的持续维持。此外，我们还讨论了转录记忆的错误面包屑线索如何为理解组蛋白修饰酶的杂合功能丧失突变如何导致严重的神经发育障碍提供了一个框架。
