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

doi:10.1016/j.omtn.2023.03.014

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

Mol Ther Nucleic Acids. 2023 Mar 24:32:385-401. doi: 10.1016/j.omtn.2023.03.014. eCollection 2023 Jun 13.

Authors

Chenchen Feng¹, Chao Song^{2

3

4}, Yong Jiang⁵, Jun Zhao¹, Jian Zhang¹, Yuezhu Wang¹, Mingxue Yin^{2

3

4}, Jiang Zhu¹, Bo Ai¹, Qiuyu Wang^{2

3

4

6

7

8}, Fengcui Qian^{2

3

4}, Yuexin Zhang^{2

3

4}, Desi Shang^{2

3

4

6

7

8}, Jiaqi Liu^{2

3

4}, Chunquan Li^{1

2

3

4

6

7

8}

Affiliations

¹ School of Medical Informatics, Daqing Campus, Harbin Medical University, Daqing 163319, China.
² The First Affiliated Hospital, Institute of Cardiovascular Disease, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China.
³ School of Computer, University of South China, Hengyang, Hunan 421001, China.
⁴ The First Affiliated Hospital, Cardiovascular Lab of Big Data and Imaging Affiliated Intelligence, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China.
⁵ Medical Research Institute, Wuhan University, Wuhan 430000, China.
⁶ The First Affiliated Hospital, Department of Cardiology, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China.
⁷ Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China.
⁸ Department of Cell Biology and Genetics, School of Basic Medical Sciences, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China.

Abstract

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.

Keywords: MT: Bioinformatics; core transcription regulatory circuitry; network analysis; platform; super enhancer; transcription factor.