Comprehensive epigenome characterization reveals diverse transcriptional regulation across human vascular endothelial cells

Endothelial cells (ECs) make up the innermost layer throughout the entire vasculature. Their phenotypes and physiological functions are initially regulated by developmental signals and extracellular stimuli. The underlying molecular mechanisms responsible for the diverse phenotypes of ECs from diffe...

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Published inbioRxiv
Main Authors Nakato, Ryuichiro, Wada, Youichiro, Nakaki, Ryo, Nagae, Genta, Katou, Yuki, Tsutsumi, Shuichi, Nakajima, Natsu, Fukuhara, Hiroshi, Izumi-Taguchi, Akashi, Kohro, Takahide, Kanki, Yasuharu, Saito, Yutaka, Kobayashi, Mika, Osato, Naoki, Tatsuno, Kenji, Kamio, Asuka, Hayashi-Takanaka, Yoko, Wada, Hiromi, Ohta, Shinzo, Aikawa, Masanori, Nakajima, Hiroyuki, Nakamura, Masaki, Mcgee, Rebecca C, Heppner, Kyle W, Kawakatsu, Tatsuo, Genno, Michiru, Yanase, Hiroshi, Kume, Haruki, Senbonmatsu, Takaaki, Homma, Yukio, Nishimura, Shigeyuki, Mituyama, Toutai, Aburatani, Hiroyuki, Kimura, Hiroshi, Shirahige, Katsuhiko
Format Paper
LanguageEnglish
Published Cold Spring Harbor Cold Spring Harbor Laboratory Press 05.09.2019
Subjects
Angiogenesis
Chromatin
Endothelial cells
Enhancers
Gene expression
Gene regulation
Genetic diversity
Genomes
Molecular modelling
Phenotypes
Transcription
Vascular system
Wound healing
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Summary:Endothelial cells (ECs) make up the innermost layer throughout the entire vasculature. Their phenotypes and physiological functions are initially regulated by developmental signals and extracellular stimuli. The underlying molecular mechanisms responsible for the diverse phenotypes of ECs from different organs are not well understood. To characterize the transcriptomic and epigenomic landscape in the vascular system, we cataloged gene expression and active histone marks in nine types of human ECs (generating 148 genome-wide datasets) and carried out a comprehensive analysis with chromatin interaction data. We identified 3,765 EC-specific enhancers, some of which were associated with disease-associated genetic variations. We also identified various candidate marker genes for each EC type. Notably, reflecting the developmental origins of ECs and their roles in angiogenesis, vasculogenesis and wound healing. While the importance of several HOX genes for early vascular development and adult angiogenesis in pathological conditions has been reported, a systematic analysis of the regulation and roles of HOX genes in mature tissue cells has been lacking. These datasets provide a valuable resource for understanding the vascular system and associated diseases. Footnotes * https://rnakato.github.io/HumanEndothelialEpigenome/
DOI:10.1101/756056