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Nucleation and spreading maintain Polycomb domains every cell cycle.

Giovana M B Veronezi1, Srinivas Ramachandran2

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Polycomb domains maintain gene repression memory through replication. New research reveals Polycomb repressive complex 2 (PRC2) targets nucleation sites post-replication, ensuring epigenetic memory is passed to daughter cells.

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Area of Science:

  • Epigenetics and Gene Regulation
  • Developmental Biology
  • Cell Biology

Background:

  • Polycomb pathway gene repression is vital for metazoan development.
  • Polycomb domains, marked by H3K27me3, require maintenance through cell division to preserve epigenetic memory.
  • Mechanisms of H3K27me3 maintenance post-replication remain largely unknown.

Purpose of the Study:

  • To elucidate how locus-specific H3K27me3 is maintained across the cell cycle.
  • To identify nucleation sites responsible for H3K27me3 domain establishment and maintenance.
  • To understand the role of Polycomb repressive complex 2 (PRC2) in H3K27me3 recovery post-replication.

Main Methods:

  • Development of CUT&Flow (coupling cleavage under target and tagmentation with flow cytometry) to map H3K27me3 dynamics.
  • Identification of nucleation sites within Polycomb domains in mouse embryonic stem cells.
  • Utilizing PRC2 subunit-specific inhibitors to assess PRC2's role in H3K27me3 maintenance.

Main Results:

  • Post-replication recovery of Polycomb domains occurs via nucleation and spreading from specific sites.
  • These nucleation sites are utilized for both de novo domain formation and maintenance.
  • PRC2 targets nucleation sites post-replication independently of pre-existing H3K27me3.

Conclusions:

  • H3K27me3 domain maintenance relies on nucleation and spreading mechanisms.
  • PRC2 plays a crucial role in targeting nucleation sites for H3K27me3 deposition post-replication.
  • A balance between H3K27me3 deposition and nucleosome turnover governs epigenetic memory during cell division.