A Non-canonical BCOR-PRC1.1 Complex Represses Differentiation Programs in Human ESCs

Cell Stem Cell. 2018 Feb 1;22(2):235-251.e9. doi: 10.1016/j.stem.2017.12.002. Epub 2018 Jan 11.


Polycomb group proteins regulate self-renewal and differentiation in many stem cell systems. When assembled into two canonical complexes, PRC1 and PRC2, they sequentially deposit H3K27me3 and H2AK119ub histone marks and establish repressive chromatin, referred to as Polycomb domains. Non-canonical PRC1 complexes retain RING1/RNF2 E3-ubiquitin ligases but have unique sets of accessory subunits. How these non-canonical complexes recognize and regulate their gene targets remains poorly understood. Here, we show that the BCL6 co-repressor (BCOR), a member of the PRC1.1 complex, is critical for maintaining primed pluripotency in human embryonic stem cells (ESCs). BCOR depletion leads to the erosion of Polycomb domains at key developmental loci and the initiation of differentiation along endoderm and mesoderm lineages. The C terminus of BCOR regulates the assembly and targeting of the PRC1.1 complex, while the N terminus contributes to BCOR-PRC1.1 repressor function. Our findings advance understanding of Polycomb targeting and repression in ESCs and could apply broadly across developmental systems.

Keywords: BCOR; human embryonic stem cells; pluripotency; polycomb repressive complexes.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Differentiation*
  • Chromatin / metabolism
  • F-Box Proteins / metabolism
  • Histones / metabolism
  • Human Embryonic Stem Cells / cytology*
  • Human Embryonic Stem Cells / metabolism*
  • Humans
  • Jumonji Domain-Containing Histone Demethylases / metabolism
  • Lysine / metabolism
  • Methylation
  • Multiprotein Complexes / metabolism*
  • Polycomb Repressive Complex 1 / metabolism*
  • Polycomb Repressive Complex 2 / metabolism
  • Promoter Regions, Genetic
  • Protein Domains
  • Proto-Oncogene Proteins / chemistry
  • Proto-Oncogene Proteins / metabolism*
  • Repressor Proteins / chemistry
  • Repressor Proteins / metabolism*


  • BCOR protein, human
  • Chromatin
  • F-Box Proteins
  • Histones
  • Multiprotein Complexes
  • Proto-Oncogene Proteins
  • Repressor Proteins
  • Jumonji Domain-Containing Histone Demethylases
  • KDM2A protein, human
  • Polycomb Repressive Complex 2
  • Polycomb Repressive Complex 1
  • RNF2 protein, human
  • Lysine