title: The core regulatory network in human cells.
abstract: In order to discover the common characteristics of various cell types in the human body, many researches have been conducted to find the set of genes commonly expressed in various cell types and tissues. However, the functional characteristics of a cell is determined by the complex regulatory relationships among the genes rather than by expressed genes themselves. Therefore, it is more important to identify and analyze a core regulatory network where all regulatory relationship between genes are active across all cell types to uncover the common features of various cell types. Here, based on hundreds of tissue-specific gene regulatory networks constructed by recent genome-wide experimental data, we constructed the core regulatory network. Interestingly, we found that the core regulatory network is organized by simple cascade and has few complex regulations such as feedback or feed-forward loops. Moreover, we discovered that the regulatory links from genes in the core regulatory network to genes in the peripheral regulatory network are much more abundant than the reverse direction links. These results suggest that the core regulatory network locates at the top of regulatory network and plays a role as a 'hub' in terms of information flow, and the information that is common to all cells can be modified to achieve the tissue-specific characteristics through various types of feedback and feed-forward loops in the peripheral regulatory networks. We also found that the genes in the core regulatory network are evolutionary conserved, essential and non-disease, non-druggable genes compared to the peripheral genes. Overall, our study provides an insight into how all human cells share a common function and generate tissue-specific functional traits by transmitting and processing information through regulatory network.
authors.affiliation: Graduate School of New Drug Discovery and Development, Chungnam National University, 99, Daehak-ro, Daejeon, 34134, Republic of Korea; Molecular Genetics and Genomics Laboratory, Department of Horticulture, College of Agriculture and Life Sciences, Chungnam National University, Daejeon, 34134, Republic of Korea. Electronic address: kms77@cnu.ac.kr.
authors.forename: Man-Sun
authors.initials: MS
authors.lastname: Kim
authors.affiliation: Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 34141, Republic of Korea. Electronic address: dongsan@kaist.ac.kr.
authors.forename: Dongsan
authors.initials: D
authors.lastname: Kim
authors.affiliation: Graduate School of New Drug Discovery and Development, Chungnam National University, 99, Daehak-ro, Daejeon, 34134, Republic of Korea. Electronic address: nskang@cnu.ac.kr.
authors.forename: Nam Sook
authors.initials: NS
authors.lastname: Kang
authors.affiliation: Department of Mathematics, University of Seoul, 163 Seoulsiripdaero, Dongdaemun-gu, Seoul, 02504, Republic of Korea. Electronic address: jrkim@uos.ac.kr.
authors.forename: Jeong-Rae
authors.initials: JR
authors.lastname: Kim
mesh_terms: D053263:Gene Regulatory Networks; D006801:Humans; D049490:Systems Biology
keywords: Common cellular function; Core regulatory network; Gene regulatory network; Network identification; Systems biology