m6A regulates heterochromatin in mammalian embryonic stem cells

As the most well-studied modification in mRNA, m⁶A has been shown to regulate multiple biological processes, including RNA degradation, processing, and translation. Recent studies showed that m⁶A modification is enriched in chromatin-associated RNAs and nascent RNAs, suggesting m⁶A might play regulatory roles in chromatin contexts. Indeed, in the past several years, a number of studies have clarified how m⁶A and its modulators regulate different types of chromatin states. Specifically, in the past 2–3 years, several studies discovered the roles of m⁶A and/or its modulators in regulating constitutive and facultative heterochromatin, shedding interesting lights on RNA-dependent heterochromatin formation in mammalian cells. This review will summarize and discuss the mechanisms underlying m⁶A’s regulation in different types of heterochromatin, with a specific emphasis on the regulation in mammalian embryonic stem cells, which exhibit distinct features of multiple heterochromatin marks.