title: EPOP Interacts with Elongin BC and USP7 to Modulate the Chromatin Landscape.
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.
authors.affiliation: Division of Newborn Medicine and Program in Epigenetics, Department of Medicine, Boston Children's Hospital, Boston, MA 02115, USA; Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Liefke
authors.affiliation: Division of Newborn Medicine and Program in Epigenetics, Department of Medicine, Boston Children's Hospital, Boston, MA 02115, USA; Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Violetta
authors.initials: V
authors.lastname: Karwacki-Neisius
authors.affiliation: Division of Newborn Medicine and Program in Epigenetics, Department of Medicine, Boston Children's Hospital, Boston, MA 02115, USA; Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA. Electronic address: yang_shi@hms.harvard.edu.
authors.forename: Yang
authors.initials: Y
authors.lastname: Shi
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D002843:Chromatin / Q000737:chemistry* / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone; D004257:DNA Polymerase II / Q000235:genetics / Q000378:metabolism; D000075065:Elongin; D004622:Embryo, Mammalian; D018507:Gene Expression Regulation, Developmental; D053263:Gene Regulatory Networks; D006657:Histones / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051379:Mice; D000066450:Mouse Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism; D063151:Polycomb Repressive Complex 2 / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic; D000076084:Ubiquitin-Specific Peptidase 7; D064570:Ubiquitin-Specific Proteases / Q000235:genetics* / Q000378:metabolism
chemical_list: D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D000075065:Elongin; C579430:Epop protein, mouse; D006657:Histones; D009419:Nerve Tissue Proteins; D014157:Transcription Factors; D063151:Polycomb Repressive Complex 2; D004257:DNA Polymerase II; D000076084:Ubiquitin-Specific Peptidase 7; D064570:Ubiquitin-Specific Proteases; C579190:Usp7 protein, mouse
keywords: Elongin BC; H2Bub; MYC; Polycomb; USP7; cancer; chromatin; pluripotency; stem cells; transcription