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Nat Commun. 2018 Aug 23;9(1):3377. doi: 10.1038/s41467-018-05728-x.

Polycomb complexes associate with enhancers and promote oncogenic transcriptional programs in cancer through multiple mechanisms.

Author information

1
Sylvester Comprehensive Cancer Center, Biomedical Research Building, 1501 NW 10th Avenue, Miami, FL, 33136, USA.
2
Department of Human Genetics, University of Miami Miller School of Medicine, Miami, FL, 33136, USA.
3
Centro de Investigaciones Médicas (CIM), Núcleo Científico Multidisciplinario, Escuela de Medicina, Universidad de Talca, Avenida Lircay S/N, Talca, 3460000, Chile.
4
Laboratory of Cellular and Structural Biology, The Rockefeller University, New York, NY, 10065, USA.
5
Institute for Systems Genetics and Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY, 10016, USA.
6
Sylvester Comprehensive Cancer Center, Biomedical Research Building, 1501 NW 10th Avenue, Miami, FL, 33136, USA. lmorey@med.miami.edu.
7
Department of Human Genetics, University of Miami Miller School of Medicine, Miami, FL, 33136, USA. lmorey@med.miami.edu.

Abstract

Polycomb repressive complex 1 (PRC1) plays essential roles in cell fate decisions and development. However, its role in cancer is less well understood. Here, we show that RNF2, encoding RING1B, and canonical PRC1 (cPRC1) genes are overexpressed in breast cancer. We find that cPRC1 complexes functionally associate with ERα and its pioneer factor FOXA1 in ER+ breast cancer cells, and with BRD4 in triple-negative breast cancer cells (TNBC). While cPRC1 still exerts its repressive function, it is also recruited to oncogenic active enhancers. RING1B regulates enhancer activity and gene transcription not only by promoting the expression of oncogenes but also by regulating chromatin accessibility. Functionally, RING1B plays a divergent role in ER+ and TNBC metastasis. Finally, we show that concomitant recruitment of RING1B to active enhancers occurs across multiple cancers, highlighting an under-explored function of cPRC1 in regulating oncogenic transcriptional programs in cancer.

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