Angiogenesis is a crucial process for organ morphogenesis and growth during development, and it is especially relevant during the repair of wounded tissue in adults. It is coordinated by an equilibrium of pro- and anti-angiogenic factors; nevertheless, when affected, it promotes several diseases. Lately, a growing body of evidence is indicating that non-coding RNAs (ncRNAs), such as miRNAs, circRNAs, and lncRNAs, play critical roles in angiogenesis. These ncRNAs can act in cis or trans and alter gene transcription by several mechanisms including epigenetic processes. In the following pages, we will discuss the functions of ncRNAs in the regulation of angiogenesis and neovascularization, both in normal and disease contexts, from an epigenetic perspective. Additionally, we will describe the contribution of Next-Generation Sequencing (NGS) techniques to the discovery and understanding of the role of ncRNAs in angiogenesis.
Every cell of an organism shares the same genome; even so, each cellular lineage owns a different transcriptome and proteome. The Polycomb group proteins (PcG) are essential regulators of gene repression patterning during development and homeostasis. However, it is unknown how the repressive complexes, PRC1 and PRC2, identify their targets and elicit new Polycomb domains during cell differentiation. Classical recruitment models consider the pre-existence of repressive histone marks; still, de novo target binding overcomes the absence of both H3K27me3 and H2AK119ub. The CpG islands (CGIs), non-core proteins, and RNA molecules are involved in Polycomb recruitment. Nonetheless, it is unclear how de novo targets are identified depending on the physiological context and developmental stage and which are the leading players stabilizing Polycomb complexes at domain nucleation sites. Here, we examine the features of de novo sites and the accessory elements bridging its recruitment and discuss the first steps of Polycomb domain formation and transcriptional regulation, comprehended by the experimental reconstruction of the repressive domains through time-resolved genomic analyses in mammals.
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