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Polycomb complexes associate with enhancers to promote oncogenic transcriptional programs in cancer

ABSTRACT: Polycomb complexes associate with enhancers to promote oncogenic transcriptional programs in cancer

PROVIDER: PRJNA419210 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR6309980.fastq.gz	Fastqsanger.gz
	SRR6309990.fastq.gz	Fastqsanger.gz
	SRR6309981.fastq.gz	Fastqsanger.gz
	SRR6309991.fastq.gz	Fastqsanger.gz
	SRR6309982.fastq.gz	Fastqsanger.gz

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Polycomb complexes associate with enhancers to promote oncogenic transcriptional programs in cancer

Project description:The Polycomb repressive complexes PRC1 and PRC2 play an essential role in cell fate decisions, embryonic development and gene regulation. While the functions of PRC2 in cancer are under intense study, the function of PRC1 in cancer remains largely unexplored. Here, we show that RNF2, the gene encoding RING1B, and canonical PRC1 (cPRC1) genes are amplified and overexpressed in breast cancer. Specifically, in estrogen receptor positive (ER+) breast cancer cells, cPRC1 is functionally associated with enhancers and genes regulated by ERa, while in triple negative breast cancer (TNBC) cells, a different cPRC1 variant is recruited to enhancers and promoters occupied by the bromodomain protein BRD4. Mechanistically, cPRC1 complexes are recruited to active enhancers independently of PRC2 and RING1B enzymatic activity. Moreover, RING1B has a dual role in regulating enhancer activity and gene transcription as it is recruited to enhancers to maintain and promote gene expression of breast cancer oncogenes. We also show that RING1B regulates chromatin accessibility of oncogenic transcription factors. Finally, we provide evidence that association of PRC1 to active enhancers is not restricted to breast cancer, demonstrating that RING1B recruitment to transcriptionally active sites occurs in multiple cancer types. Our work highlights a non-classical function of cPRC1 complexes in regulating specific oncogenic programs in cancer through its association with enhancer regions.

2018-08-30 | GSE107176 | GEO

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

Project description: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 ER? 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.

| S-EPMC6107513 | biostudies-literature

Polycomb complexes in skin epithelium development

Project description:Polycomb complexes in skin epithelium development

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Mapping polycomb complexes in human and mouse embryonic stem cells

Project description:In embryonic stem (ES) cells, bivalent chromatin domains with overlapping repressive (H3 lysine 27 tri-methylation) and activating (H3 lysine 4 tri-methylation) histone modifications mark the promoters of more than 2000 genes. To gain insight into the structure and function of bivalent domains, we mapped key histone modifications and subunits of Polycomb repressive complexes 1 and 2 (PRC1 and PRC2) genomewide in human and mouse ES cells by chromatin immunoprecipitation followed by ultra high-throughput sequencing. We find that bivalent domains can be segregated into two classes: the first occupied by both PRC2 and PRC1 (PRC1-positive) and the second specifically bound by PRC2 (PRC2-only). PRC1-positive bivalent domains appear functionally distinct as they more efficiently retain lysine 27 tri-methylation upon differentiation, show stringent conservation of chromatin state, and associate with an overwhelming number of developmental regulator gene promoters. We also used computational genomics to search for sequence determinants of Polycomb binding. This analysis revealed that the genomewide locations of PRC2 and PRC1 can be largely predicted from the locations, sizes and underlying motif contents of CpG islands. We propose that large CpG islands depleted of activating motifs confer epigenetic memory by recruiting the full repertoire of Polycomb complexes. Keywords: cell type comparison Suz12, Ezh2, Ring1b ChIP-Seq in singlicate from mouse embryonic stem (mES) cells. H3K4me3, H3K27me3, H3K36me3, Ezh2 and Ring1b ChIP-Seq in singlicate from human embyonic stem cells (hES; H9).

2008-11-01 | E-GEOD-13084 | biostudies-arrayexpress

Polycomb complexes in skin epithelium development II

Project description:Polycomb group (PcG) proteins are essential epigenetic transcriptional regulators. Traditionally, PcG proteins function as two multi-subunit complexes, Polycomb repressive complex 1 (PRC1) and PRC2, which largely overlap in their genomic binding and cooperate to establish repressive chromatin domains demarcated by H2AK119ub and H3K27me3. Here, using the developing skin epidermis as a paradigm, we uncovered a functional redundancy between Polycomb complexes in the repression of unwanted non-lineage genes.

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Polycomb complexes in skin epithelium development III

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Polycomb complexes in skin epithelium development III

Project description:Polycomb complexes in skin epithelium development III

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Polycomb complexes in skin epithelium development II

Project description:Polycomb complexes in skin epithelium development II

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Polycomb complexes in skin epithelium development I