Diverse heterochromatin states restricting cell identity and reprogramming

Heterochromatin is defined as a chromosomal domain harboring repressive H3K9me2/3 or H3K27me3 histone modifications and relevant factors that physically compact the chromatin. Heterochromatin can restrict where transcription factors bind, providing a barrier to gene activation and changes in cell identity. While heterochromatin thus helps maintain cell differentiation, it presents a barrier to overcome during efforts to reprogram cells for biomedical purposes. Recent findings have revealed complexity in the composition and regulation of heterochromatin, and shown that transiently disrupting the machinery of heterochromatin can enhance reprogramming. Here, we discuss how heterochromatin is established and maintained during development, and how our growing understanding of the mechanisms regulating H3K9me3 heterochromatin can be leveraged to improve our ability to direct changes in cell identity.

Automated summary

Heterochromatin is a chromosomal region that contains repressive histone modifications and factors that compact the chromatin, thus limiting the binding of transcription factors and inhibiting gene activation and cell identity changes. While important for cell differentiation, heterochromatin presents challenges in cell reprogramming. Recent studies have shown that transient disruption of heterochromatin machinery can enhance reprogramming. This review discusses the establishment and maintenance of heterochromatin during development and explores how the regulation of H3K9me3 heterochromatin can improve our ability to direct cell identity changes.