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Polycomb group and SCF ubiquitin ligases are found in a novel BCOR complex that is recruited to BCL6 targets

Micah D Gearhart1, Connie M Corcoran, Joseph A Wamstad

  • 1Department of Genetics, Cell Biology and Development, 6-160 Jackson Hall, 321 Church Street SE, Minneapolis, MN 55455, USA.

Molecular and Cellular Biology
|September 1, 2006
PubMed

Insights

The BCOR complex, containing Polycomb group proteins and E3 ubiquitin ligases, is recruited by BCL6 to target genes. This complex mediates epigenetic modifications for gene silencing, offering insights into male-lethal syndromes.

Area of Science:

  • Epigenetics
  • Molecular Biology
  • Genetics

Background:

  • The corepressor BCOR interacts with the proto-oncoprotein BCL6 and suppresses AF9 transcriptional activity.
  • Mutations in BCOR are linked to male lethal, X-linked oculofaciocardiodental syndrome.

Purpose of the Study:

  • To elucidate the molecular mechanisms of the BCOR complex in transcriptional repression.
  • To investigate the role of BCOR in recruiting epigenetic modifiers to BCL6 target genes.

Main Methods:

  • Co-immunoprecipitation to identify BCOR complex components.
  • Localization studies of BCOR complex proteins and modified histones at BCL6 target genes.
  • Analysis of histone demethylase activity associated with the BCOR complex.

Main Results:

  • Identified a BCOR complex containing Polycomb group (PcG) proteins (RING1, RYBP, NSPC1, RNF2) and Skp-Cullin-F-box (SCF) subcomplex components (SKP1, FBXL10).
  • Demonstrated that BCOR complex components and mono-ubiquitylated H2A localize to BCL6 targets.
  • Showed that FBXL10, a component of the BCOR complex, possesses histone H3K36 demethylase activity.

Conclusions:

  • The BCOR complex utilizes PcG proteins to expand BCL6's enzymatic recruitment repertoire, suggesting BCL6 can target PcG proteins to DNA.
  • BCOR complex recruitment of two distinct E3 ubiquitin ligases and a histone demethylase indicates a unique combination of epigenetic modifications for gene silencing.
  • Findings provide insights into the molecular basis of BCOR-related disorders and gene regulation.

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