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.

中文翻译：

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Hansel、Gretel 和未能去除组蛋白甲基化面包屑的后果。

就像森林中的面包屑一样，共转录获得的组蛋白甲基化充当先前转录的记忆。因为它可以通过细胞分裂保留下来，转录记忆允许细胞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期间没有正确重新编程，它也会破坏细胞身份。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期间组蛋白甲基化重编程失败的后果：受精时的母体重编程、胚胎干细胞 (ESC) 分化和分化细胞中细胞身份的持续维持。此外，