EPOP Interacts with Elongin BC and USP7 to Modulate the Chromatin Landscape

Mol Cell. 2016 Nov 17;64(4):659-672. doi: 10.1016/j.molcel.2016.10.019.

Abstract

Gene regulatory networks are pivotal for many biological processes. In mouse embryonic stem cells (mESCs), the transcriptional network can be divided into three functionally distinct modules: Polycomb, Core, and Myc. The Polycomb module represses developmental genes, while the Myc module is associated with proliferative functions, and its mis-regulation is linked to cancer development. Here, we show that, in mESCs, the Polycomb repressive complex 2 (PRC2)-associated protein EPOP (Elongin BC and Polycomb Repressive Complex 2-associated protein; a.k.a. C17orf96, esPRC2p48, and E130012A19Rik) co-localizes at chromatin with members of the Myc and Polycomb module. EPOP interacts with the transcription elongation factor Elongin BC and the H2B deubiquitinase USP7 to modulate transcriptional processes in mESCs similar to MYC. EPOP is commonly upregulated in human cancer, and its loss impairs the proliferation of several human cancer cell lines. Our findings establish EPOP as a transcriptional modulator, which impacts both Polycomb and active gene transcription in mammalian cells.

Keywords: Elongin BC; H2Bub; MYC; Polycomb; USP7; cancer; chromatin; pluripotency; stem cells; transcription.

Publication types

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

MeSH terms

  • Animals
  • Cell Differentiation
  • Cell Line, Tumor
  • Chromatin / chemistry*
  • Chromatin / metabolism
  • DNA Polymerase II / genetics
  • DNA Polymerase II / metabolism
  • Elongin
  • Embryo, Mammalian
  • Gene Expression Regulation, Developmental*
  • Gene Regulatory Networks
  • Histones / genetics
  • Histones / metabolism
  • Humans
  • Mice
  • Mouse Embryonic Stem Cells / cytology
  • Mouse Embryonic Stem Cells / metabolism
  • Nerve Tissue Proteins / genetics*
  • Nerve Tissue Proteins / metabolism
  • Pluripotent Stem Cells / cytology
  • Pluripotent Stem Cells / metabolism
  • Polycomb Repressive Complex 2 / genetics*
  • Polycomb Repressive Complex 2 / metabolism
  • Promoter Regions, Genetic
  • Protein Binding
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism
  • Transcription, Genetic
  • Ubiquitin-Specific Peptidase 7
  • Ubiquitin-Specific Proteases / genetics*
  • Ubiquitin-Specific Proteases / metabolism

Substances

  • Chromatin
  • E13 protein, mouse
  • Elongin
  • Histones
  • Nerve Tissue Proteins
  • Transcription Factors
  • Polycomb Repressive Complex 2
  • DNA Polymerase II
  • Ubiquitin-Specific Peptidase 7
  • Ubiquitin-Specific Proteases
  • Usp7 protein, mouse