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Disruption of PRC1 Components RING1A and RING1B Promotes Angiogenesis via Relieving BMP4 Repression [RNA-Seq]

ABSTRACT: Angiogenesis is crucial for maintaining tissue homeostasis and responding to injury and disease. Epigenetic mechanisms have been elucidated to regulate the expression of pro-angiogenic factors and modulate angiogenesis. The Polycomb repressive complex 1 (PRC1) is a key epigenetic repressive complex that regulates multiple biological functions. Within this complex, RING1A and RING1B, which serve as the E3 ubiquitin ligases for PRC1, contribute to the monoubiquitylation of histone H2A on Lysine 119 (H2AK119ub), thereby repressing gene transcription. However, the role of RING1A and RING1B in regulating angiogenesis has remained elusive. In this study, we demonstrate that RING1A and RING1B suppress angiogenic capacity in vitro, although they do not inhibit migration and proliferation in endothelial cells (ECs). Furthermore, by integrating RNA sequencing data from RING1A knockdown or RING1B knockdown ECs with CUT&Tag assay results for RING1A, RING1B, and H2AK119ub in ECs, we have identified that PRC1 inhibits angiogenesis by repressing BMP4 expression, a pro-angiogenic factor known to regulate angiogenesis. Additionally, we verify that the knockdown of RING1A and RING1B enhances angiogenesis in vivo, which may provide a new therapeutic target for angiogenesis-related diseases.

ORGANISM(S): Homo sapiens

PROVIDER: GSE281872 | GEO | 2025/07/24

REPOSITORIES: GEO

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Disruption of PRC1 Components RING1A and RING1B Promotes Angiogenesis via Relieving BMP4 Repression [CUT&Tag]

Project description:Angiogenesis is crucial for maintaining tissue homeostasis and responding to injury and disease. Epigenetic mechanisms have been elucidated to regulate the expression of pro-angiogenic factors and modulate angiogenesis. The Polycomb repressive complex 1 (PRC1) is a key epigenetic repressive complex that regulates multiple biological functions. Within this complex, RING1A and RING1B, which serve as the E3 ubiquitin ligases for PRC1, contribute to the monoubiquitylation of histone H2A on Lysine 119 (H2AK119ub), thereby repressing gene transcription. However, the role of RING1A and RING1B in regulating angiogenesis has remained elusive. In this study, we demonstrate that RING1A and RING1B suppress angiogenic capacity in vitro, although they do not inhibit migration and proliferation in endothelial cells (ECs). Furthermore, by integrating RNA sequencing data from RING1A knockdown or RING1B knockdown ECs with CUT&Tag assay results for RING1A, RING1B, and H2AK119ub in ECs, we have identified that PRC1 inhibits angiogenesis by repressing BMP4 expression, a pro-angiogenic factor known to regulate angiogenesis. Additionally, we verify that the knockdown of RING1A and RING1B enhances angiogenesis in vivo, which may provide a new therapeutic target for angiogenesis-related diseases.

2025-07-24 | GSE281870 | GEO

The Central Role of EED in the Orchestration of Polycomb Group Complexes

Project description:Polycomb Repressive Complexes 1 and 2 (PRC1 and 2) play a critical role in the epigenetic regulation of transcription during cellular differentiation, stem cell pluripotency, and neoplastic progression1-3. Here we show that the Polycomb group protein EED, a core component of PRC2, physically interacts with and functions as part of the PRC1 complex. Components of PRC1 and PRC2 compete for EED binding. EED functions to recruit PRC1 to H3K27me3 loci and enhances PRC1 mediated H2A ubiquitin E3 ligase activity. Taken together, we uncover the integral role of EED as an epigenetic exchange factor coordinating the activities of PRC1 and 2. EED, uH2A, RING1A, RING1B, BMI1 and H3K27Me3 ChIP-seq in EED stable knockdown and control Scramble DU145 prostate cancer cell line

2014-01-23 | E-GEOD-42566 | biostudies-arrayexpress

Transcription profiling of mouse embryonic stem cells FROM Eed knockout vs control

Project description:The Polycomb group (PcG) gene products mediate heritable silencing of developmental regulators in metazoans, participating in one of two distinct multimeric protein complexes, the Polycomb repressive complexes-1 (PRC1) and -2 (PRC2). PRC2 catalyses trimethylation of histone H3 at lysine 27 (H3K27) which in turn is thought to provide a recruitment site for PRC1. Recent studies demonstrate that mono-ubiquitylation of histone H2A at lysine 119 is important in PcG mediated silencing with the core PRC1 component Ring1A/B functioning as the E3 ligase8. PRC2 has been shown to share target genes with the core transcription network to maintain embryonic stem (ES) cells including Oct4 and Nanog. Here we identify an essential role for PRC1 in repressing developmental regulators in ES cells, and thereby in maintaining ES cell pluripotency. A significant proportion of the PRC1 target genes are also repressed by Oct4. We demonstrate that engagement of PRC1 and PRC2 at target genes is Oct4-dependent and moreover that Ring1B interacts with Oct4. Collectively these results show that PcG complexes are instrumental in Oct4-dependent repression required to maintain pluripotency of ES cells. This study provides a first functional link between a core ES cell regulator and global epigenetic regulation of the genome. Experiment Overall Design: Eed is a protein included in PRC2 (Polycomb repressor complex). Experiment Overall Design: We generated constitutive Eed KO mouse ES cells and observed gene expression using Affymetrix MOE430.2 microarray. Experiment Overall Design: These results were compared with other KO cells of PRC1 proteins (Ring1A, Ring1B) and other proteins in our study.

2008-04-07 | E-GEOD-10574 | biostudies-arrayexpress

Ring1A and Ring1B maintain murine MOZ-TIF2 AML stem cells by inhibiting expression of Glis2

Project description:Eradication of chemotherapy-resistant leukemia stem cells is expected to improve treatment outcomes in patients with acute myelogenous leukemia (AML). In a mouse model of AML expressing the MOZ-TIF2 fusion, we found that Ring1A and Ring1B, components of Polycomb repressive complex 1, play crucial roles in maintaining AML stem cells. Deletion of Ring1A and Ring1B (Ring1A/B) from MOZ-TIF2 AML cells diminished self-renewal capacity and induced the expression of numerous genes including Gli-similar 2 (Glis2). Overexpression of Glis2 caused MOZ-TIF2 AML cells to differentiate into mature cells, whereas Glis2 knockdown in Ring1A/B-deficient MOZ-TIF2 cells inhibited differentiation. Thus, Ring1A/B regulates and maintains AML stem cells in part by repressing Glis2 expression, which promotes their differentiation. These findings provide new insights into the mechanism of AML stem cell homeostasis and reveal novel targets for cancer stem cell therapy.

2017-01-06 | GSE93214 | GEO

Transcription profiling of mouse Ring1B single and Ring1A/B double knockout cells shows Ring1B interacts with Oct4.

Project description:The Polycomb group (PcG) gene products mediate heritable silencing of developmental regulators in metazoans, participating in one of two distinct multimeric protein complexes, the Polycomb repressive complexes-1 (PRC1) and -2 (PRC2)1-5. PRC2 catalyses trimethylation of histone H3 at lysine 27 (H3K27) which in turn is thought to provide a recruitment site for PRC13-7. Recent studies demonstrate that mono-ubiquitylation of histone H2A at lysine 119 is important in PcG mediated silencing with the core PRC1 component Ring1A/B functioning as the E3 ligase8. PRC2 has been shown to share target genes with the core transcription network to maintain embryonic stem (ES) cells including Oct4 and Nanog9. Here we identify an essential role for PRC1 in repressing developmental regulators in ES cells, and thereby in maintaining ES cell pluripotency. A significant proportion of the PRC1 target genes are also repressed by Oct4. We demonstrate that engagement of PRC1 and PRC2 at target genes is Oct4-dependent and moreover that Ring1B interacts with Oct4. Collectively these results show that PcG complexes are instrumental in Oct4-dependent repression required to maintain pluripotency of ES cells. This study provides a first functional link between a core ES cell regulator and global epigenetic regulation of the genome. Experiment Overall Design: We observed gene expression of Ring1B single and Ring1A/B double KO cells using Affymetrix chip: MOE 430 2.0. Experiment Overall Design: Because constitutive Ring1A/B-dKO cells can not be maintained we generated conditional KO cells with OHT.

2008-04-07 | E-GEOD-10476 | biostudies-arrayexpress

Next-Generation Sequencing Facilitates Quantitative Analysis of WT, Ring1a-/-, Ring1b-/-, Ring1a/b-/-, Pcgf1/3/5/6-/- and Pcgf1/2/3/4/5/6-/- Embryonic Stem Cells Transcriptomes

Project description:Polycomb repressive complexes (PRC) are epigenetic transcriptional repressors by establishing facultative heterochromatin repressive domains and play an essential role in numerous developmental processes. PRC1, which contains the E3 ligases RING1A/B and deposits H2AK119ub, forms six biochemically subcomplexes (PRC1.1-PRC1.6) based on the assembled PCGF protein (PCGF1–PCGF6), and has been involved in the maintenance of embryonic stem (ES) cell state. More recent evidence indicates that PCGF family participates in the self-renewal and pluripotent maintenance. However, it is still enigmatic that how the PCGF family engaged in the controlling process. Here, we generate the Ring1a-/-, Ring1b-/-, Ring1a/b-/-, Pcgf1/3/5/6-/- and Pcgf1/2/3/4/5/6-/- ES cells using CRISPR/Cas9 technique and CRE-LoxP recombination system to discover the central determinants in PCGF family-related biological process.

2022-09-01 | GSE183646 | GEO

Expression data from Ring1A(-/-);Ring1B(fl/fl);R26::CreERT2 ES cells expressing either of mock, WT or mutant Ring1B construct before or after OHT treatment

Project description:We used microarrays to investigate the restoration of repression of PRC1 target gene expression in Ring1A/B-dKO ES cells stably expressing either of mock, WT or mutant Ring1B construct.

2012-06-11 | GSE38224 | GEO

PCGF Homologs and RYBP Define Functionally Distinct PRC1 Family Complexes

Project description:The heterogeneous nature of mammalian PRC1 complexes has hindered our understanding of their biological functions. Here, we present a comprehensive proteomic and genomic analysis that uncovered six major groups of PRC1 complexes each containing a distinct PCGF subunit, a RING1A/B ubiquitin ligase, and a unique set of associated polypeptides. These PRC1 complexes differ in their genomic localization and only a small subset co-localize with H3K27me3. Further biochemical dissection revealed that the six PCGF–RING1A/B combinations form multiple complexes through association with RYBP or its homolog YAF2, which prevents the incorporation of other canonical PRC1 subunits such as CBX, PHC and SCM. Although both RYBP/YAF2- and CBX/PHC/SCM-containing complexes compact chromatin, only RYBP stimulates the activity of RING1B toward H2AK119ub1, suggesting a central role in PRC1 function. Knockdown of RYBP in ES cells compromised their ability to form embryoid bodies, likely because of defects in cell proliferation and maintenance of H2AK119ub1 level.

2012-02-09 | GSE34774 | GEO

Wound memory of epidermal stem cells [scRNAseq L1 PRT]

Project description:Wound priming in epidermal Lrig1 stem cell progeny leads to a more efficient response to future injuries. To identify a key epigenetic factor of this cellular adaptation, we performed an epigenetic drug screening in Lrig1 genetically labled mice. Pre-treatment with PRT4165 lead to a more efficient wound closure. To understand if PRT4165 was able to recapitulate wound priming, we performed single cell RNA-seq transcriptome profiling of epidermal Lrig1 stem cell progenies from PRT4165-treated or untreated murine skin. [PRT4165is an inhibitor of the enzymatic activity of Ring1a/Ring1b, component of the Polycomb repressive complexes 1 (PRC1), responsible for the monoubiquitination of lysin 119 on histone H2A (H2AK119ub)]

2023-02-02 | GSE197586 | GEO

Non-canonical PRC1.1 targets active genes independent of H3K27me3 and is essential for leukemogenesis

Project description:Polycomb proteins are classical regulators of stem cell self-renewal and cell lineage commitment and are frequently deregulated in cancer. Here we find that the non-canonical PRC1.1 complex, as identified by mass spectrometry-based proteomics, is critically important for human leukemic stem cells. Downmodulation of PRC1.1 complex members, like the DNA-binding subunit KDM2B, strongly reduces cell proliferation in vitro and delays or even abrogates leukemogenesis in vivo in humanized xenograft models. PRC1.1 components are significantly overexpressed in primary AML CD34+ cells. Besides a set of genes that is co-targeted by PRC1 and PRC2, ChIP-seq studies show that PRC1.1 also binds a distinct set of genes that are devoid of H3K27me3 suggesting a gene regulatory role independent of PRC2. This set encompasses genes involved in metabolism, which have transcriptionally active chromatin profiles. These data indicate that PRC1.1 controls distinct gene clusters involved in unique cell biological processes required for leukemic cell viability. K562 cells were transduced with lentiviral GFP-fusion vectors encoding GFP-CBX2, PCGF1-GPF, PCGF2-GFP, PCGF4-GFP, GFP-RING1A or GFP-RING1B. K562 cells expressing GFP-fusions at relatively low levels were sorted and expanded and subsequently crosslinked. ChIP reactions were performed using the following antibodies: anti-GFP (ab290, Abcam), anti-H3K27me3 (07-449, Millipore), anti-H3K4me3 (ab8580, Abcam), anti-H2AK119ub (D27C4, Cell Signaling Technology), and anti-KDM2B (ab137547, Abcam). Furthermore, ChIP reactions were performed using primary AML CD34+ and Peripheral Blood (PB) CD34+ cells using anti-H3K27me3 (07-449, Millipore), anti-H3K4me3 (ab8580, Abcam), anti-H2AK119ub (D27C4, Cell Signaling Technology), anti-KDM2B (ab137547, Abcam).

2015-11-24 | E-GEOD-54580 | biostudies-arrayexpress

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