Cohesin Disrupts Polycomb-Dependent Chromosome Interactions in Embryonic Stem Cells

Area of Science:

• Epigenetics and Chromosome Biology
• Gene Regulation and Genome Organization

Background:

• The relationship between chromosome organization and genome function is not fully understood.
• Cohesin, loop extrusion, and CCCTC-binding factor (CTCF) are implicated in forming topologically associating domains (TADs) that regulate gene expression.

Purpose of the Study:

• To investigate the role of cohesin in chromosome conformation and gene regulation in embryonic stem cells.
• To identify cohesin-independent chromosomal interactions and their regulatory mechanisms.

Main Methods:

• Analysis of chromosome conformation in embryonic stem cells lacking cohesin.
• Investigation of polycomb repressive system (PRC) and PRC1-dependent interactions.
• Assessment of cohesin's effect on polycomb-dependent interactions and super-enhancer interactions.

Main Results:

• Cohesin is required for TAD formation and A/B compartmentalization in embryonic stem cells.
• Cohesin-deficient cells exhibit persistent long-range chromosomal interactions dependent on the polycomb repressive system and PRC1.
• Cohesin counteracts polycomb-dependent interactions, independent of CTCF and insulation, modulating gene repression.

Conclusions:

• Cohesin plays a crucial role in establishing higher-order chromosome structure and regulating gene expression in embryonic stem cells.
• Cohesin actively disrupts polycomb-mediated chromosomal interactions, thereby fine-tuning gene repression.
• These findings reveal a novel mechanism by which cohesin modulates gene expression through antagonizing polycomb-dependent genome organization.