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Angiogenesis is extensively involved in embryonic development and requires complex regulation networks, whose defects can cause a variety of vascular abnormalities. Cis-regulatory elements control gene expression at all developmental stages, but they have not been studied or profiled in angiogenesis yet. In this study, we exploited public DNase-seq and RNA-seq datasets from a VEGFA-stimulated in vitro angiogenic model, and carried out an integrated analysis of the transcriptome and chromatin accessibility across the entire process. Totally, we generated a bank of 47,125 angiogenic cis-regulatory elements with promoter (marker by H3K4me3) and/or enhancer (marker by H3K27ac) activities. Motif enrichment analysis revealed that these angiogenic cis-regulatory elements interacted preferentially with ETS family TFs. With this tool, we performed an association study using our WES data of TAPVC and identified rs199530718 as a cis-regulatory SNP associated with disease risk. Altogether, this study generated a genome-wide bank of angiogenic cis-regulatory elements and illustrated its utility in identifying novel cis-regulatory SNPs for TAPVC, expanding new horizons of angiogenesis as well as vascular abnormality genetics.

Titel:	Genome-wide profiling of angiogenic cis-regulatory elements unravels cis-regulatory SNPs for vascular abnormality.
Autor/in / Beteiligte Person:	Jin, L ; Han, Z ; Mao, X ; Lu, J ; Yan, B ; Lu, Y ; Liang, L ; Wang, L ; Yu, Y ; Sun, K
Link:	View record at Springer (Volltext)
Zeitschrift:	Scientific data, Jg. 11 (2024-05-08), Heft 1, S. 467
Veröffentlichung:	London : Nature Publishing Group, 2014-, 2024
Medientyp:	academicJournal
ISSN:	2052-4463 (electronic)
DOI:	10.1038/s41597-024-03272-6
Schlagwort:	Humans Regulatory Sequences, Nucleic Acid Vascular Endothelial Growth Factor A genetics Genome-Wide Association Study Neovascularization, Pathologic genetics Polymorphism, Single Nucleotide
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article; Research Support, Non-U.S. Gov't; Dataset Language: English [Sci Data] 2024 May 08; Vol. 11 (1), pp. 467. <i>Date of Electronic Publication: </i>2024 May 08. MeSH Terms: Polymorphism, Single Nucleotide* ; Humans ; Regulatory Sequences, Nucleic Acid ; Vascular Endothelial Growth Factor A / genetics ; Genome-Wide Association Study ; Neovascularization, Pathologic / genetics References: Sci Data. 2024 May 8;11(1):467. (PMID: 38719891) ; Front Cardiovasc Med. 2019 Mar 28;6:30. (PMID: 30984768) ; Nat Cell Biol. 2017 Aug;19(8):915-927. (PMID: 28714968) ; Cell. 2001 Jun 29;105(7):863-75. (PMID: 11439183) ; Cell. 2016 Jun 2;165(6):1375-1388. (PMID: 27259149) ; Mol Metab. 2016 Jan 11;5(3):233-244. (PMID: 26977395) ; Curr Biol. 2011 Oct 25;21(20):1759-65. (PMID: 22000107) ; Genome Res. 2019 Feb;29(2):193-207. (PMID: 30670628) ; Nat Biotechnol. 2010 May;28(5):495-501. 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(PMID: 36568976) Grant Information: 82170304 National Natural Science Foundation of China (National Science Foundation of China); 82170304 National Natural Science Foundation of China (National Science Foundation of China) Substance Nomenclature: 0 (Vascular Endothelial Growth Factor A) Entry Date(s): Date Created: 20240508 Date Completed: 20240508 Latest Revision: 20240513 Update Code: 20240514 PubMed Central ID: PMC11078952

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Genome-wide profiling of angiogenic cis-regulatory elements unravels cis-regulatory SNPs for vascular abnormality.