Polycomb complexes associate with enhancers and promote oncogenic transcriptional programs in cancer through multiple mechanisms.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 30139998.
- Also identified by DOI 10.1038/s41467-018-05728-x and PMC identifier 6107513.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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.
Medical subject headings
- Breast Neoplasms
- Gene Expression Regulation, Neoplastic
- Polycomb Repressive Complex 1
- Regulatory Sequences, Nucleic Acid