Landscape and significance of human super enhancer-driven core transcription regulatory circuitry

Chenchen Feng; Chao Song; Yong Jiang; Jun Zhao; Jian Zhang; Yuezhu Wang; Mingxue Yin; Jiang Zhu; Bo Ai; Qiuyu Wang; Fengcui Qian; Yuexin Zhang; Desi Shang; Jiaqi Liu; Chunquan Li

Molecular Therapy: Nucleic Acids (Jun 2023)

Landscape and significance of human super enhancer-driven core transcription regulatory circuitry

Chenchen Feng,
Chao Song,
Yong Jiang,
Jun Zhao,
Jian Zhang,
Yuezhu Wang,
Mingxue Yin,
Jiang Zhu,
Bo Ai,
Qiuyu Wang,
Fengcui Qian,
Yuexin Zhang,
Desi Shang,
Jiaqi Liu,
Chunquan Li

Affiliations

Chenchen Feng: School of Medical Informatics, Daqing Campus, Harbin Medical University, Daqing 163319, China
Chao Song: The First Affiliated Hospital, Institute of Cardiovascular Disease, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China; School of Computer, University of South China, Hengyang, Hunan 421001, China; The First Affiliated Hospital, Cardiovascular Lab of Big Data and Imaging Affiliated Intelligence, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China
Yong Jiang: Medical Research Institute, Wuhan University, Wuhan 430000, China
Jun Zhao: School of Medical Informatics, Daqing Campus, Harbin Medical University, Daqing 163319, China
Jian Zhang: School of Medical Informatics, Daqing Campus, Harbin Medical University, Daqing 163319, China
Yuezhu Wang: School of Medical Informatics, Daqing Campus, Harbin Medical University, Daqing 163319, China
Mingxue Yin: The First Affiliated Hospital, Institute of Cardiovascular Disease, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China; School of Computer, University of South China, Hengyang, Hunan 421001, China; The First Affiliated Hospital, Cardiovascular Lab of Big Data and Imaging Affiliated Intelligence, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China
Jiang Zhu: School of Medical Informatics, Daqing Campus, Harbin Medical University, Daqing 163319, China
Bo Ai: School of Medical Informatics, Daqing Campus, Harbin Medical University, Daqing 163319, China
Qiuyu Wang: The First Affiliated Hospital, Institute of Cardiovascular Disease, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China; School of Computer, University of South China, Hengyang, Hunan 421001, China; The First Affiliated Hospital, Cardiovascular Lab of Big Data and Imaging Affiliated Intelligence, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China; The First Affiliated Hospital, Department of Cardiology, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China; Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China; Department of Cell Biology and Genetics, School of Basic Medical Sciences, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China
Fengcui Qian: The First Affiliated Hospital, Institute of Cardiovascular Disease, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China; School of Computer, University of South China, Hengyang, Hunan 421001, China; The First Affiliated Hospital, Cardiovascular Lab of Big Data and Imaging Affiliated Intelligence, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China
Yuexin Zhang: The First Affiliated Hospital, Institute of Cardiovascular Disease, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China; School of Computer, University of South China, Hengyang, Hunan 421001, China; The First Affiliated Hospital, Cardiovascular Lab of Big Data and Imaging Affiliated Intelligence, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China
Desi Shang: The First Affiliated Hospital, Institute of Cardiovascular Disease, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China; School of Computer, University of South China, Hengyang, Hunan 421001, China; The First Affiliated Hospital, Cardiovascular Lab of Big Data and Imaging Affiliated Intelligence, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China; The First Affiliated Hospital, Department of Cardiology, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China; Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China; Department of Cell Biology and Genetics, School of Basic Medical Sciences, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China
Jiaqi Liu: The First Affiliated Hospital, Institute of Cardiovascular Disease, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China; School of Computer, University of South China, Hengyang, Hunan 421001, China; The First Affiliated Hospital, Cardiovascular Lab of Big Data and Imaging Affiliated Intelligence, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China
Chunquan Li: School of Medical Informatics, Daqing Campus, Harbin Medical University, Daqing 163319, China; The First Affiliated Hospital, Institute of Cardiovascular Disease, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China; School of Computer, University of South China, Hengyang, Hunan 421001, China; The First Affiliated Hospital, Cardiovascular Lab of Big Data and Imaging Affiliated Intelligence, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China; The First Affiliated Hospital, Department of Cardiology, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China; Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China; Department of Cell Biology and Genetics, School of Basic Medical Sciences, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China; Corresponding author: Chunquan Li, School of Medical Informatics, Daqing Campus, Harbin Medical University, Daqing 163319, China.

Journal volume & issue: Vol. 32
pp. 385 – 401

Abstract

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A core transcription regulatory circuitry (CRC) is an interconnected self-regulatory circuitry that is formed by a group of core transcription factors (TFs). These core TFs collectively regulate gene expression by binding not only to their own super enhancers (SEs) but also to the SEs of one another. For most human tissue/cell types, a global view of CRCs and core TFs has not been generated. Here, we identified numerous CRCs using two identification methods and detailed the landscape of the CRCs driven by SEs in large cell/tissue samples. The comprehensive biological analyses, including sequence conservation, CRC activity and genome binding affinity were conducted for common TFs, moderate TFs, and specific TFs, which exhibit different biological features. The local module located from the common CRC network highlighted the essential functions and prognostic performance. The tissue-specific CRC network was highly related to cell identity. Core TFs in tissue-specific CRC networks exhibited disease markers, and had regulatory potential for cancer immunotherapy. Moreover, a user-friendly resource named CRCdb (http://www.licpathway.net/crcdb/index.html) was developed, which contained the detailed information of CRCs and core TFs used in this study, as well as other interesting results, such as the most representative CRC, frequency of TFs, and indegree/outdegree of TFs.

Published in Molecular Therapy: Nucleic Acids

ISSN: 2162-2531 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Therapeutics. Pharmacology
Website: https://www.cell.com/molecular-therapy-family/nucleic-acids/latest-content

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