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

Nature Communications
Ho Lam ChanLluis 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.

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Citations

Feb 23, 2019·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Vincent LoubiereGiacomo Cavalli
Jun 7, 2019·The Journal of Biological Chemistry·Joshua K StoneEun-Young Erin Ahn
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Oct 14, 2021·Nature Communications·Aida Ferreiro-IglesiasPaul Brennan

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Datasets Mentioned

BETA
GSE107176
PXD009570

Methods Mentioned

BETA
immunoprecipitation
ChIP-seq
RNA-seq
mono-ubiquitination
co-immunoprecipitations
transfection
transfections
xenografts
FACS
PCR

Software Mentioned

Enrichr
Adobe Illustrator CC
BWA
Living Image
UCSC genome browser
Bowtie2
CFX Manager
GDCquery
GDCdownload
BEDtools

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