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PRC2 binds active promoters and contacts nascent RNAs in embryonic stem cells

Syuzo Kaneko1, Jinsook Son, Steven S Shen

  • 11] Howard Hughes Medical Institute, New York University School of Medicine, New York, New York, USA. [2] Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, New York, USA.

Nature Structural & Molecular Biology
|October 22, 2013
PubMed

Insights

Enhancer of Zeste Homolog 2 (EZH2) binds nascent RNA to regulate epigenetic marks during cell differentiation. This mechanism allows PRC2 to sense transcriptional states and modify gene expression.

Area of Science:

  • Epigenetics
  • Molecular Biology
  • Developmental Biology

Background:

  • Polycomb Repressive Complex 2 (PRC2) is a key epigenetic repressor.
  • EZH2 is the catalytic subunit of PRC2, crucial for development and stem cell differentiation.
  • The regulation and targeting of PRC2 to specific genes are not well understood.

Purpose of the Study:

  • To investigate how PRC2 is regulated and directed to specific genes.
  • To elucidate the mechanism by which PRC2 interacts with the genome during differentiation.
  • To understand the role of EZH2 in sensing cellular transcriptional states.

Main Methods:

  • In vivo RNA-protein cross-linking in mouse embryonic stem cells (ESCs).
  • Analysis of PRC2 binding to promoters and nascent RNAs.
  • Correlation of EZH2 binding with H3K27me3 levels.

Main Results:

  • PRC2 binds at low levels to most promoters in mouse ESCs, including active ones.
  • EZH2 directly binds the 5' region of nascent RNAs from a subset of promoters.
  • EZH2-nascent RNA binding correlates with reduced H3K27me3 marks.

Conclusions:

  • PRC2 can sense the transcriptional state of a cell.
  • EZH2-nascent RNA interaction provides a mechanism for targeting PRC2.
  • This interaction translates transcriptional information into epigenetic modifications.

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