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.
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.
Project description:These data include RNA Seq data generated from wild type and Ring1a Ring1b dKO ISCs from Lgr5Gfp-CreERT2, Lgr5Gfp-CreERT2 Ring1a-/- Ring1bf/f, Lgr5Gfp-CreERT2-Ctnnb1-ex3 and Lgr5Gfp-CreERT2 Ring1a-/- Ring1bf/f-Ctnnb1-ex3 mice. Total RNA extracted from sorted wild type and Ring1a Ring1b dKO ISCs.
Project description:These data include RNA Seq data generated from wild type and Ring1a Ring1b dKO Villi from Rosa26-CreERT2 Cdkn2a-/- and Rosa26-CreERT2 Cdkn2a-/- Ring1a-/- Ring1bf/f mice. Total RNA extracted from wild type and Ring1a Ring1b dKO Villi.
Project description:H3K4me1 (ab8895 Abcam) and H3K27ac (ab4729 Abcam) antibodies were used for ChIP-seq in Ring1a-/- mouse ES cells and after 48h tamoxifen treatment in conditional knock-out of Ring1b in the Ring1a -/- background.
Project description:These data include RNA Seq data generated from Ring1b wild type and Ring1b KO Ring1a-/- Cdkn2a-/- Lin- HSC cells non-transduced or transduced with MLL-AF9, HOXA9 and PML-RARa. Total RNA extracted from Ring1b wild type and Ring1b KO Ring1a-/- Cdkn2a-/- Lin- HSC cells non-transduced or transduced with MLL-AF9, HOXA9 and PML-RARa.
Project description:These data include RNA Seq data generated from wild type and Ring1a Ring1b dKO ISCs from Lgr5Gfp-CreERT2, Lgr5Gfp-CreERT2 Ring1a-/- Ring1bf/f, Lgr5Gfp-CreERT2-Ctnnb1-ex3 and Lgr5Gfp-CreERT2 Ring1a-/- Ring1bf/f-Ctnnb1-ex3 mice.
Project description:These data include RNA Seq data generated from wild type and Ring1a Ring1b dKO Villi from Rosa26-CreERT2 Cdkn2a-/- and Rosa26-CreERT2 Cdkn2a-/- Ring1a-/- Ring1bf/f mice.
Project description:We examined the dynamic changes of H3K27me3 and gene expression in neocortical neural stem cells directly isolated from various stages of embryonic brains. ChIP-seq of HMGA2 protein in the early stage of neural stem cell, and transcriptome analysis of Ring1A-/-;Ring1Bf/f and Ring1A-/-;Ring1B-/- were also performed.
