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

Author

Listed:
  • Ho Lam Chan

    (Sylvester Comprehensive Cancer Center
    University of Miami Miller School of Medicine)

  • Felipe Beckedorff

    (Sylvester Comprehensive Cancer Center
    University of Miami Miller School of Medicine)

  • Yusheng Zhang

    (Sylvester Comprehensive Cancer Center
    University of Miami Miller School of Medicine)

  • Jenaro Garcia-Huidobro

    (Sylvester Comprehensive Cancer Center
    University of Miami Miller School of Medicine
    Escuela de Medicina, Universidad de Talca)

  • Hua Jiang

    (The Rockefeller University)

  • Antonio Colaprico

    (Sylvester Comprehensive Cancer Center
    University of Miami Miller School of Medicine)

  • Daniel Bilbao

    (Sylvester Comprehensive Cancer Center)

  • Maria E. Figueroa

    (Sylvester Comprehensive Cancer Center
    University of Miami Miller School of Medicine)

  • John LaCava

    (The Rockefeller University
    New York University School of Medicine)

  • Ramin Shiekhattar

    (Sylvester Comprehensive Cancer Center
    University of Miami Miller School of Medicine)

  • Lluis Morey

    (Sylvester Comprehensive Cancer Center
    University of Miami Miller School of Medicine)

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.

Suggested Citation

  • Ho Lam Chan & Felipe Beckedorff & Yusheng Zhang & Jenaro Garcia-Huidobro & Hua Jiang & Antonio Colaprico & Daniel Bilbao & Maria E. Figueroa & John LaCava & Ramin Shiekhattar & Lluis Morey, 2018. "Polycomb complexes associate with enhancers and promote oncogenic transcriptional programs in cancer through multiple mechanisms," Nature Communications, Nature, vol. 9(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-05728-x
    DOI: 10.1038/s41467-018-05728-x
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    Cited by:

    1. Daniel Bsteh & Hagar F. Moussa & Georg Michlits & Ramesh Yelagandula & Jingkui Wang & Ulrich Elling & Oliver Bell, 2023. "Loss of cohesin regulator PDS5A reveals repressive role of Polycomb loops," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    2. Aida Ferreiro-Iglesias & James D. McKay & Nicole Brenner & Shama Virani & Corina Lesseur & Valerie Gaborieau & Andy R. Ness & Rayjean J. Hung & Geoffrey Liu & Brenda Diergaarde & Andrew F. Olshan & Ne, 2021. "Germline determinants of humoral immune response to HPV-16 protect against oropharyngeal cancer," Nature Communications, Nature, vol. 12(1), pages 1-11, December.

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