Comprehensive epigenome characterization reveals diverse transcriptional regulation across human vascular endothelial cells.,Epigenetics & Chromatin

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Comprehensive epigenome characterization reveals diverse transcriptional regulation across human vascular endothelial cells.
Epigenetics & Chromatin ( IF 3.9 ) Pub Date : 2019-12-19 , DOI: 10.1186/s13072-019-0319-0
Ryuichiro Nakato _{1,

2} , Youichiro Wada _{2,

3} , Ryo Nakaki ₄ , Genta Nagae _{2,

4} , Yuki Katou ₅ , Shuichi Tsutsumi ₄ , Natsu Nakajima ₁ , Hiroshi Fukuhara ₆ , Atsushi Iguchi ₇ , Takahide Kohro ₈ , Yasuharu Kanki _{2,

3} , Yutaka Saito _{2,

9,

10} , Mika Kobayashi ₃ , Akashi Izumi-Taguchi ₃ , Naoki Osato _{2,

4} , Kenji Tatsuno ₄ , Asuka Kamio ₄ , Yoko Hayashi-Takanaka _{2,

11} , Hiromi Wada _{3,

12} , Shinzo Ohta ₁₂ , Masanori Aikawa ₁₃ , Hiroyuki Nakajima ₇ , Masaki Nakamura ₆ , Rebecca C McGee ₁₄ , Kyle W Heppner ₁₄ , Tatsuo Kawakatsu ₁₅ , Michiru Genno ₁₅ , Hiroshi Yanase ₁₅ , Haruki Kume ₆ , Takaaki Senbonmatsu ₁₆ , Yukio Homma ₆ , Shigeyuki Nishimura ₁₆ , Toutai Mitsuyama _{2,

9} , Hiroyuki Aburatani _{2,

4} , Hiroshi Kimura _{2,

11,

17} , Katsuhiko Shirahige _{2,

5}

Affiliation

Laboratory of Computational Genomics, Institute for Quantitative Biosciences, The University of Tokyo, Tokyo, 113-0032, Japan.
Japan Agency for Medical Research and Development (AMED-CREST), AMED, 1-7-1 Otemachi, Chiyoda-ku, Tokyo, 100-0004, Japan.
Isotope Science Center, The University of Tokyo, Tokyo, 113-0032, Japan.
Genome Science Division, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo, 153-8904, Japan.
Laboratory of Genome Structure and Function, Institute for Quantitative Biosciences, The University of Tokyo, Tokyo, 113-0032, Japan.
Department of Urology, Graduate School of Medicine, The University of Tokyo, Tokyo, 113-8655, Japan.
Department of Cardiovascular Surgery, Saitama Medical University International Medical Center, Saitama, 350-1298, Japan.
Department of Clinical Informatics, Jichi Medical University School of Medicine, Shimotsuke, 329-0498, Japan.
Artificial Intelligence Research Center, National Institute of Advanced Industrial Science and Technology (AIST), 2-4-7 Aomi, Koto-ku, Tokyo, 135-0064, Japan.
Computational Bio Big-Data Open Innovation Laboratory (CBBD-OIL), National Institute of Advanced Industrial Science and Technology (AIST), 3-4-1 Okubo, Shinjuku-ku, Tokyo, 169-8555, Japan.
Cell Biology Center, Institute of Innovative Research, Tokyo Institute of Technology, Yokohama, 226-8503, Japan.
Brain Attack Center, Ohta Memorial Hospital, Fukuyama, 720-0825, Japan.
The Center for Excellence in Vascular Biology and the Center for Interdisciplinary Cardiovascular Sciences, Cardiovascular Division and Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA.
Lifeline Cell Technology, Frederick, MD, 21701, USA.
Bio-Medical Department, Kurabo Industries Ltd., Neyagawa, Osaka, 572-0823, Japan.
Department of Cardiology, Saitama Medical University International Medical Center, Saitama, 350-1298, Japan.
Laboratory of Functional Nuclear Imaging, Institute for Quantitative Biosciences, The University of Tokyo, Tokyo, 113-0032, Japan.

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.

更新日期：2020-04-22

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