EPOP Functionally Links Elongin and Polycomb in Pluripotent Stem Cells.

Area of Science:

• Cell Biology
• Epigenetics
• Stem Cell Biology

Background:

• Pluripotent stem cells exhibit cellular plasticity, sustained by genomic regions with dual active and repressive chromatin states.
• The mechanisms controlling low gene expression at these bivalent sites remain largely unknown.

Purpose of the Study:

• To identify factors involved in regulating gene expression at bivalent sites in pluripotent stem cells.
• To elucidate the role of Elongin BC and its associated proteins in maintaining chromatin states.

Main Methods:

• Biochemical analyses to identify protein interactions.
• Genome-wide analyses to map factor occupancy and gene expression.
• Studies using knockout/knockdown approaches to assess protein function.

Main Results:

• Elongin BC binds to the promoters of bivalent genomic sites.
• Elongin BC forms a complex with Polycomb Repressive Complex 2 (PRC2) in pluripotent stem cells.
• The PRC2-associated factor EPOP recruits Elongin BC to chromatin.
• Both EPOP and Elongin BC are essential for maintaining low expression at PRC2 target genes.

Conclusions:

• Elongin BC and EPOP play a critical role in regulating gene expression at PRC2 targets in pluripotent stem cells.
• The balance of activating and repressive cues is a fundamental aspect of chromatin regulation in pluripotency.