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Prediction and Validation of Gene Regulatory Elements Activated During Retinoic Acid Induced Embryonic Stem Cell Differentiation
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Prediction and Validation of Gene Regulatory Elements Activated During Retinoic Acid Induced Embryonic Stem Cell Differentiation

Published on: June 21, 2016

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Coordinated regulation of retinoic acid signaling pathway by KDM5B and polycomb repressive complex 2

Yu Zhang1, Jing Liang, Qian Li

  • 1Department of Biochemistry and Molecular Biology, Peking University Health Science Center, Beijing, 100191, China.

Journal of Cellular Biochemistry
|March 13, 2014
PubMed

Insights

KDM5B associates with Polycomb repressive complex 2 (PRC2) to regulate retinoic acid signaling. This interaction is crucial for gene expression, impacting cell identity and disease.

Area of Science:

  • Epigenetics
  • Molecular Biology
  • Gene Regulation

Background:

  • Polycomb repressive complex 2 (PRC2) is a key epigenetic regulator involved in cell identity, stem cell renewal, and differentiation.
  • Dysregulation of PRC2 is frequently observed in human cancers and various diseases.
  • KDM5B, a histone lysine demethylase, is implicated in cellular processes but its interaction with PRC2 was not well understood.

Purpose of the Study:

  • To investigate the functional relationship between KDM5B and PRC2.
  • To elucidate the role of KDM5B in retinoic acid (RA) signaling.
  • To understand the molecular mechanisms underlying KDM5B and PRC2 cooperation in gene regulation.

Main Methods:

  • Co-immunoprecipitation and colocalization studies to assess KDM5B-PRC2 interaction.
  • In vitro pull-down assays and transcription readout experiments to determine KDM5B's role in RA signaling.
  • Chromatin immunoprecipitation (ChIP) assays to analyze KDM5B and PRC2 occupancy and histone modifications (H3K4me3) at target genes.

Main Results:

  • KDM5B physically associates with PRC2, specifically interacting with the SUZ12 component, and colocalizes in nuclear bodies.
  • KDM5B acts as a co-activator, not a co-repressor, in RA signaling, with its JMJC domain crucial for interaction with retinoic acid receptor α (RARα).
  • KDM5B exhibits a biphasic effect on RA-induced gene activation, involving H3K4me3 demethylation and antagonism of PRC2 activity.

Conclusions:

  • KDM5B and PRC2 cooperate to regulate the retinoic acid signaling pathway.
  • The physical and functional interplay between KDM5B and PRC2 is essential for orchestrated gene expression.
  • These findings reveal a novel mechanism of epigenetic regulation in RA signaling with implications for understanding cell identity maintenance and disease.
Keywords:
HISTONE MODIFICATIONKDM5BPRC2RARRETINOIC ACID

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