TY - JOUR
T1 - Polycomb complexes associate with enhancers and promote oncogenic transcriptional programs in cancer through multiple mechanisms
AU - Chan, Ho Lam
AU - Beckedorff, Felipe
AU - Zhang, Yusheng
AU - Garcia-Huidobro, Jenaro
AU - Jiang, Hua
AU - Colaprico, Antonio
AU - Bilbao, Daniel
AU - Figueroa, Maria E.
AU - LaCava, John
AU - Shiekhattar, Ramin
AU - Morey, Lluis
N1 - Funding Information:
We are indebted to V.A. Raker for help in preparing the manuscript, to Gloria Mas Martin and Dr. Joyce M. Slingerland for discussions, and to the Oncogenomics Core Facility at the Sylvester Comprehensive Cancer Center for performing high-throughput sequencing. We also thank the Flow Cytometry Core Facility for assistance with cell sorting, and the Cancer Modeling Shared Resource for assistance with the animal studies. Dr. Ramiro E. Verdun kindly provided the shRING1B plasmids. Kelly Molloy assisted with the mass spectrometry. Dr. Derek M. Dykxhoorn assisted with the iPSC culture. Dr. Aznar-Benitah provided the pMSCV-IRES-Luciferase-GFP vector. This work was supported by Sylvester Comprehensive Cancer Center funds to L.M.
Publisher Copyright:
© 2018, The Author(s).
PY - 2018/12/1
Y1 - 2018/12/1
N2 - 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.
AB - 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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U2 - 10.1038/s41467-018-05728-x
DO - 10.1038/s41467-018-05728-x
M3 - Article
C2 - 30139998
AN - SCOPUS:85052240843
VL - 9
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
IS - 1
M1 - 3377
ER -