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Functional analysis of AEBP2, a PRC2 Polycomb protein, reveals a Trithorax phenotype in embryonic development and in ESCs.

Development (Cambridge, England) | 2016

The Polycomb repressive complexes PRC1 and PRC2 are key mediators of heritable gene silencing in multicellular organisms. Here, we characterise AEBP2, a known PRC2 co-factor which, in vitro, has been shown to stimulate PRC2 activity. We show that AEBP2 localises specifically to PRC2 target loci, including the inactive X chromosome. Proteomic analysis confirms that AEBP2 associates exclusively with PRC2 complexes. However, analysis of embryos homozygous for a targeted mutation of Aebp2 unexpectedly revealed a Trithorax phenotype, normally linked to antagonism of Polycomb function. Consistent with this, we observe elevated levels of PRC2-mediated histone H3K27 methylation at target loci in Aebp2 mutant embryonic stem cells (ESCs). We further demonstrate that mutant ESCs assemble atypical hybrid PRC2 subcomplexes, potentially accounting for enhancement of Polycomb activity, and suggesting that AEBP2 normally plays a role in defining the mutually exclusive composition of PRC2 subcomplexes.

Pubmed ID: 27317809 RIS Download

Research resources used in this publication

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Antibodies used in this publication

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Associated grants

  • Agency: British Heart Foundation, United Kingdom
    Id: PG/07/045/22690
  • Agency: Wellcome Trust, United Kingdom
    Id: WT103768AIA
  • Agency: Medical Research Council, United Kingdom
    Id: G0900747 91070
  • Agency: British Heart Foundation, United Kingdom
    Id: RG/10/17/28553
  • Agency: Wellcome Trust, United Kingdom
    Id: 090019/Z/09/A
  • Agency: European Research Council, International
    Id: 340081
  • Agency: Wellcome Trust, United Kingdom
  • Agency: Wellcome Trust, United Kingdom
    Id: 081385

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