Heterochromatin organization and phase separation

ABSTRACT

The eukaryotic nucleus displays a variety of membraneless compartments with distinct biomolecular composition and specific cellular activities. Emerging evidence indicates that protein-based liquid–liquid phase separation (LLPS) plays an essential role in the formation and dynamic regulation of heterochromatin compartmentalization. This feature is especially conspicuous at the pericentric heterochromatin domains. In this review, we will describe our understanding of heterochromatin organization and LLPS. In addition, we will highlight the increasing importance of multivalent weak homo- and heteromolecular interactions in LLPS-mediated heterochromatin compartmentalization in the complex environment inside living cells.

KEYWORDS:

• DNA methylation
• heterochromatin
• histone H1
• histone modifications
• HP1
• liquid-liquid phase separation
• MeCP2
• RNA binding proteins
• X chromosome inactivation

Acknowledgments

We thank the past and present members of our laboratories as well as our collaborators for their contributions over the past years.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

Our work was funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) grants CA 198/10-1 project number 326470517 and CA 198/16-1 project number 425470807 to M.C.C., HL 721/18-1 project number 425470807 and SFB 1064 project number 213249687 to H.L.