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

Ryuichiro Nakato, Youichiro Wada*, Ryo Nakaki, Genta Nagae, Yuki Katou, Shuichi Tsutsumi, Natsu Nakajima, Hiroshi Fukuhara, Atsushi Iguchi, Takahide Kohro, Yasuharu Kanki, Yutaka Saito, Mika Kobayashi, Akashi Izumi-Taguchi, Naoki Osato, Kenji Tatsuno, Asuka Kamio, Yoko Hayashi-Takanaka, Hiromi Wada, Shinzo OhtaMasanori Aikawa, Hiroyuki Nakajima, Masaki Nakamura, Rebecca C. McGee, Kyle W. Heppner, Tatsuo Kawakatsu, Michiru Genno, Hiroshi Yanase, Haruki Kume, Takaaki Senbonmatsu, Yukio Homma, Shigeyuki Nishimura, Toutai Mitsuyama, Hiroyuki Aburatani, Hiroshi Kimura, Katsuhiko Shirahige

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)

Abstract

Background: 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. Results: 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 developed a robust procedure for comparative epigenome analysis that circumvents variations at the level of the individual and technical noise derived from sample preparation under various conditions. Through this approach, we identified 3765 EC-specific enhancers, some of which were associated with disease-associated genetic variations. We also identified various candidate marker genes for each EC type. We found that the nine EC types can be divided into two subgroups, corresponding to those with upper-body origins and lower-body origins, based on their epigenomic landscape. Epigenomic variations were highly correlated with gene expression patterns, but also provided unique information. Most of the deferentially expressed genes and enhancers were cooperatively enriched in more than one EC type, suggesting that the distinct combinations of multiple genes play key roles in the diverse phenotypes across EC types. Notably, many homeobox genes were differentially expressed across EC types, and their expression was correlated with the relative position of each organ in the body. This reflects the developmental origins of ECs and their roles in angiogenesis, vasculogenesis and wound healing. Conclusions: This comprehensive analysis of epigenome characterization of EC types reveals diverse transcriptional regulation across human vascular systems. These datasets provide a valuable resource for understanding the vascular system and associated diseases.

Original languageEnglish
Article number77
JournalEpigenetics and Chromatin
Volume12
Issue number1
DOIs
Publication statusPublished - 2019 Dec 19
Externally publishedYes

Keywords

  • ChIP-seq
  • Endothelial cells
  • Epigenome database
  • Histone modifications
  • Large-scale analysis

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics

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