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

Ho Lam Chan, Felipe Beckedorff, Yusheng Zhang, Jenaro Garcia-Huidobro, Hua Jiang, Antonio Colaprico, Daniel Bilbao, Maria E. Figueroa, John LaCava, Ramin Shiekhattar and Lluis Morey ()
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Ho Lam Chan: Sylvester Comprehensive Cancer Center
Felipe Beckedorff: Sylvester Comprehensive Cancer Center
Yusheng Zhang: Sylvester Comprehensive Cancer Center
Jenaro Garcia-Huidobro: Sylvester Comprehensive Cancer Center
Hua Jiang: The Rockefeller University
Antonio Colaprico: Sylvester Comprehensive Cancer Center
Daniel Bilbao: Sylvester Comprehensive Cancer Center
Maria E. Figueroa: Sylvester Comprehensive Cancer Center
John LaCava: The Rockefeller University
Ramin Shiekhattar: Sylvester Comprehensive Cancer Center
Lluis Morey: Sylvester Comprehensive Cancer Center

Nature Communications, 2018, vol. 9, issue 1, 1-16

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-018-05728-x

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