Through the lens of phase separation: intrinsically unstructured protein and chromatin looping

ABSTRACT

The establishment, maintenance and dynamic regulation of three-dimensional (3D) chromatin structures provide an important means for partitioning of genome into functionally distinctive domains, which helps to define specialized gene expression programs associated with developmental stages and cell types. Increasing evidence supports critical roles for intrinsically disordered regions (IDRs) harbored within transcription factors (TFs) and chromatin-modulatory proteins in inducing phase separation, a phenomenon of forming membrane-less condensates through partitioning of biomolecules. Such a process is also critically involved in the establishment of high-order chromatin structures and looping. IDR- and phase separation-driven 3D genome (re)organization often goes wrong in disease such as cancer. This review discusses about recent advances in understanding how phase separation of intrinsically disordered proteins (IDPs) modulates chromatin looping and gene expression.

KEYWORDS:

• Phase separation
• three-dimensional chromatin structure
• intrinsically disordered proteins (IDPs)
• intrinsically disordered regions (IDRs)
• DNA looping
• CTCF
• cohesin
• enhancer-promoter interaction
• loop extrusion
• cancer

Acknowledgments

We thank the members of Wang and Cai Laboratories for useful suggestion and discussion.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported in part by R01CA262903 (to L.C.) and R01CA271603 (to G.G.W.) and UNC Lineberger Cancer Center UCRF Stimulus Initiative Grants (to L.C.). G.G.W. is a Leukemia and Lymphoma Society (LLS) Scholar.