Disruption of PRC1 Components RING1A and RING1B Promotes Angiogenesis via Relieving BMP4 Repression [RNA-Seq]
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. Overall design: To investigate the roles of RING1A and RING1B in the regulation of angiogenesis, we developed human umbilical vein endothelial cells (HUVECs) in which both target genes were selectively knocked down using specific siRNAs. Subsequently, we conducted gene expression profiling analysis based on RNA-seq data obtained from three distinct cell lines. This involved comparing the gene expression profiles from RNA-seq data of HUVECs with those of their knockdown (KD) derivatives, specifically the RING1A KD and RING1B KD cells.