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Non-coding RNA LEVER sequestration of PRC2 can mediate long range gene regulation

Wei Wen Teo1, Xinang Cao1,2, Chan-Shuo Wu1

  • 1Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.

Communications Biology
|April 12, 2022
PubMed

Insights

A novel long non-coding RNA, LEVER, interacts with Polycomb Repressive Complex 2 (PRC2), inhibiting its function locally. This interaction regulates neighboring gene expression, specifically impacting ε-globin.

Area of Science:

  • Epigenetics
  • Molecular Biology
  • Genomics

Background:

  • Polycomb Repressive Complex 2 (PRC2) is a key epigenetic regulator for gene silencing during development.
  • The role of RNA binding by PRC2 in its biological function remains debated.
  • Understanding PRC2-RNA interactions is crucial for deciphering gene regulation.

Purpose of the Study:

  • To investigate the gene-regulatory role of inhibitory PRC2-RNA interactions.
  • To elucidate the function of a newly identified nuclear long non-coding RNA (lncRNA) named LEVER.
  • To explore how nascent RNA-PRC2 interactions influence local and neighboring gene expression.

Main Methods:

  • Nanopore sequencing to map the LEVER lncRNA.
  • Analysis of PRC2 interaction with nascent LEVER RNA.
  • Chromatin accessibility assays.
  • Assessment of histone modifications (H3K27).
  • Chromatin conformation capture techniques.

Main Results:

  • A nuclear lncRNA, LEVER, was identified upstream of the β-globin cluster.
  • LEVER RNA interacts with nascent PRC2, preventing H3K27 methylation at the LEVER locus.
  • Accessible LEVER chromatin suppresses interactions between the ε-globin locus and the β-globin locus control region (LCR).
  • This leads to repression of ε-globin gene expression.

Conclusions:

  • Nascent RNA-PRC2 interaction locally inhibits PRC2 function.
  • This local inhibition can subsequently regulate the expression of neighboring genes.
  • LEVER serves as a model for RNA-mediated regulation of PRC2 activity and gene expression.

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