Polycomb protein RYBP facilitates super-enhancer activity
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ABSTRACT:
PROVIDER: PRJNA1183812 | ENA |
REPOSITORIES: ENA
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Project description:Background Polycomb proteins are conventionally known as global repressors in cell fate determination. However, recent observations have shown their involvement in transcriptional activation, the mechanisms of which need to be further revealed. Methods Herein, multiple data from ChIP-seq, RNA-seq and HiChIP before or after RYBP depletion in embryonic stem cell (ESC), epidermal progenitor (EPC) and mesodermal cell (MEC) were analyzed. Results We found that Polycomb protein RYBP occupies at super-enhancer (SE) in ESCs, where core Polycomb group (PcG) components such as RING1B and EZH2 are minimally enriched. Depletion of RYBP results in impaired deposition of H3K27ac, decreased expression of SE-associated genes, and reducing the transcription of enhancer RNA at SE regions (seRNA). Regarding the mechanism of seRNA transcription, the Trithorax group (TrxG) component WDR5 co-localizes with RYBP at SEs, and is required for seRNA expression. RYBP depletion reduces WDR5 deposition at SE regions. In addition, TrxG-associated H3K4me3 tends to be enriched at the SEs with high levels of seRNA transcription, and RYBP deficiency impairs the deposition of H3K4me3 at SEs. Structurally, RYBP is involved in both intra- and inter-SE interactions. Finally, RYBP generally localizes at SEs in EPCs and MECs, dysfunction of RYBP is associated with various cancers and developmental diseases. Conclusion RYBP cooperates with TrxG component to regulate SE activity. Dysfunction of RYBP relates to various diseases. The findings provide new insights into the transcriptionally active function of Polycomb protein in cell fate determination.
2024-11-13 | GSE281406 | GEO
Project description:Polycomb repressive complexes (PRCs) are important chromatin regulators of ES cell function. RYBP binds Polycomb H2A monoubiquitin ligases Ring1A and Ring1B, and has been suggested to participate in localizing Polycomb complexes to their targets. Moreover, constitutive inactivation of RYBP precludes ES cell formation. Here we have used ES cells conditionally deficient in RYBP to investigate RYBP function. Chromosome immunoprecipitation on a chip (ChIP-chip) of RYBP and microarray experiments were performed using wild type and knocked-out ES cells. Gene expression profiling of WT, conditionally deficient in RYBP with or without Yaf2 RNAi, and ChIP-chip of RYBP on promoters of WT, Dnmt1-KO or Eed-KO ES cells.
2012-04-03 | E-GEOD-32294 | biostudies-arrayexpress
Project description:Here we apply integrated epigenomic and transcriptomic profiling to uncover super-enhancer heterogeneity between breast cancer subtypes, and provide clinically relevant biological insights towards TNBC. Using CRISPR/Cas9-mediated gene editing, we identify genes that are specifically regulated by TNBC-specific super-enhancers, including FOXC1 and MET, thereby unveiling a mechanism for specific overexpression of the key oncogenes in TNBC. We also identify ANLN as a novel TNBC-specific gene regulated by super-enhancer. Our studies reveal a TNBC-specific epigenomic landscape, contributing to the dysregulated oncogene expression in breast tumorigenesis.
2021-03-04 | PXD024505 |
Project description:The selective expression is pivotal in orchestrating human development, with the Trithorax Group (TrxG) and Polycomb Group (PcG) complexes playing crucial roles in transcriptional activation and repression, respectively. However, mechanism underlying selective regulation of transcription by TrxG and PcG remains poorly understood. In this study, RYBP was observed to interact with TrxG and PcG components. RYBP and TrxG co-localized loci selectively enriches RING1B. STAT3 enriches at RYBP-TrxG co-localized loci devoid of RING1B, while displaying minimal enrichment at RING1B-enrichred loci. Introduction of STAT3 at RYBP loci disrupted RING1B aggregation and chromatin binding. RYBP-deficiency impairs TrxG deposition at DNA repair genes in RYBP-TrxG loci, consequently diminishing their expression and inducing DNA damage. These results facilitate the transition of embryonic stem cells to 2-cell-like cells. Additionally, RYBP-deficiency attenuates PcG deposition at lineage-specific genes within RYBP-TrxG-RING1B loci, thereby promoting ESC differentiation. Collectively, these results provide novel insights into the selective regulation of gene expression.
2024-04-26 | GSE261485 | GEO
Project description:Polycomb repressive complexes (PRCs) are important chromatin regulators of ES cell function. RYBP binds Polycomb H2A monoubiquitin ligases Ring1A and Ring1B, and has been suggested to participate in localizing Polycomb complexes to their targets. Moreover, constitutive inactivation of RYBP precludes ES cell formation. Here we have used ES cells conditionally deficient in RYBP to investigate RYBP function. Chromosome immunoprecipitation on a chip (ChIP-chip) of RYBP and microarray experiments were performed using wild type and knocked-out ES cells. This SuperSeries is composed of the SubSeries listed below.
2012-04-04 | GSE32294 | GEO
Project description:Polycomb repressive complex 1 (PRC1) comprises two different complexes: CBX-containing canonical PRC1 (cPRC1) and RYBP/YAF2-containing variant PRC1 (vPRC1). RYBP-vPRC1 or YAF2-vPRC1 catalyzes H2AK119ub through a positive-feedback model; however, whether RYBP and YAF2 have different regulatory functions is still unclear. Here, we show that the expression of RYBP and YAF2 decreases and increases, respectively, during neural differentiation of embryonic stem cells (ESCs). Rybp knockout impairs neural differentiation by activating Wnt signaling and derepressing nonneuroectoderm-associated genes. However, Yaf2 knockout promotes neural differentiation and leads to redistribution of RYBP binding, increases enrichment of RYBP and H2AK119ub on the RYBP-YAF2 cotargeted genes, and prevents ectopic derepression of nonneuroectoderm-associated genes in neural-differentiated cells. Taken together, this study reveals that RYBP and YAF2 function differentially in regulating mESC neural differentiation.
2023-10-07 | GSE213416 | GEO
Project description:We assessed the levels of the PRC1 Polycomb mark, RYBP, H2AK119Ub1, and the PRC2 Polycomb mark, H3K27me3, considering the extensive crosstalk between PRC1 and PRC2 activities.
2023-07-06 | GSE208687 | GEO
Project description:Enhancer and super-enhancer landscape in ADPKD
| PRJNA836927 | ENA
Project description:enhancer and super-enhancer landscape in ADPKD
| PRJNA781663 | ENA
Project description:Super-enhancers comprise of dense transcription factor platforms highly enriched for active chromatin marks. A paucity of functional data led us to investigate their role in the mammary gland, an organ characterized by exceptional gene regulatory dynamics during pregnancy. ChIP-Seq for the master regulator STAT5, the glucocorticoid receptor, H3K27ac and MED1, identified 440 mammary-specific super-enhancers, half of which were associated with genes activated during pregnancy. We interrogated the Wap super-enhancer, generating mice carrying mutations in STAT5 binding sites within its three constituent enhancers. Individually, only the most distal site displayed significant enhancer activity. However, combinatorial mutations showed that the 1,000-fold gene induction relied on all enhancers. Disabling the binding sites of STAT5, NFIB and ELF5 in the proximal enhancer incapacitated the entire super-enhancer, suggesting an enhancer hierarchy. The identification of mammary-specific super-enhancers and the mechanistic exploration of the Wap locus provide insight into the complexity of cell-specific and hormone-regulated genes. ChIP-Seq for STAT5A, GR, H3K27ac, MED1, NFIB, ELF5, RNA Pol II, and H3K4me3 in wild type (WT) mammary tissues at day one of lactation (L1), and ChIP-Seq for STAT5A, GR, H3K27ac, MED1, NFIB, ELF5, and H3K4me3 in WT mammary tissues at day 13 of pregnancy (p13). ChIP-Seq for STAT5A, GR, H3K27a in Wap-delE1a, -delE1b, -delE1c, -delE2 and -delE3 mutant mammary tissues at L1, and ChIP-Seq for NFIB and ELF5 in Wap-delE1b and -delE1c mutant mammary tissues at L1. ChIP-Seq for H3K4me3 in mammary-epthelial cells at p13 and L1. DNase-seq in WT mammary tissues at L1 and DNase-seq in Wap-delE1a, -delE1c, and -delE3 mutant mammary tissues at L1.
2016-05-31 | E-GEOD-74826 | biostudies-arrayexpress