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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2018-12

AUTHORS

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

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. More... »

PAGES

3377

References to SciGraph publications

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41467-018-05728-x

    DOI

    http://dx.doi.org/10.1038/s41467-018-05728-x

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1106199476

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/30139998


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