Structural analysis of an active fungal PRC2

Area of Science:

• Biochemistry
• Structural Biology
• Molecular Biology

Background:

• Polycomb Repressive Complex 2 (PRC2) is crucial for gene silencing via histone H3K27 trimethylation (H3K27me3).
• Understanding PRC2's structural mechanisms is vital for deciphering epigenetic regulation.
• Previous studies provided foundational structural data for PRC2.

Purpose of the Study:

• To determine the crystal structure of active fungal PRC2 from Chaetomium thermophilum.
• To elucidate structural mechanisms of PRC2 assembly, catalysis, and regulation.
• To compare fungal and human PRC2 structures for insights into functional conservation and divergence.

Main Methods:

• Crystal structure determination of fungal PRC2.
• Analysis of surface conservation and electrostatic potential distribution.
• Comparison of basal and H3K27me3-stimulated PRC2 states.

Main Results:

• Revealed structural mechanisms for PRC2 assembly, catalysis, and regulation.
• Identified a conformational change in the SET domain during PRC2 activation.
• Provided insights into functional similarity and divergence between fungal and human PRC2.
• Suggested potential roles in nucleic acid binding.

Conclusions:

• The study provides a detailed structural basis for PRC2 function in H3K27me3 modification and gene silencing.
• A conserved conformational change mechanism in the SET domain underlies PRC2 regulation and allosteric stimulation.
• Findings enhance understanding of epigenetic regulation by PRC2 and related enzymes.