Determinants of transcription factor regulatory range

Chen-Hao Chen, Rongbin Zheng, Collin Tokheim, Xin Dong, Jingyu Fan, Changxin Wan, Qin Tang, Myles Brown, Jun S. Liu, Clifford A. Meyer () and X. Shirley Liu ()
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Chen-Hao Chen: Dana-Farber Cancer Institute. Harvard T.H. Chan School of Public Health
Rongbin Zheng: Clinical Translational Research Center, Shanghai Pulmonary Hospital, School of Life Sciences and Technology, Tongji University
Collin Tokheim: Dana-Farber Cancer Institute. Harvard T.H. Chan School of Public Health
Xin Dong: Clinical Translational Research Center, Shanghai Pulmonary Hospital, School of Life Sciences and Technology, Tongji University
Jingyu Fan: Clinical Translational Research Center, Shanghai Pulmonary Hospital, School of Life Sciences and Technology, Tongji University
Changxin Wan: Clinical Translational Research Center, Shanghai Pulmonary Hospital, School of Life Sciences and Technology, Tongji University
Qin Tang: Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute
Myles Brown: Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute
Jun S. Liu: Harvard University
Clifford A. Meyer: Dana-Farber Cancer Institute. Harvard T.H. Chan School of Public Health
X. Shirley Liu: Dana-Farber Cancer Institute. Harvard T.H. Chan School of Public Health

Nature Communications, 2020, vol. 11, issue 1, 1-15

Abstract: Abstract Characterization of the genomic distances over which transcription factor (TF) binding influences gene expression is important for inferring target genes from TF chromatin immunoprecipitation followed by sequencing (ChIP-seq) data. Here we systematically examine the relationship between thousands of TF and histone modification ChIP-seq data sets with thousands of gene expression profiles. We develop a model for integrating these data, which reveals two classes of TFs with distinct ranges of regulatory influence, chromatin-binding preferences, and auto-regulatory properties. We find that the regulatory range of the same TF bound within different topologically associating domains (TADs) depend on intrinsic TAD properties such as local gene density and G/C content, but also on the TAD chromatin states. Our results suggest that considering TF type, binding distance to gene locus, as well as chromatin context is important in identifying implicated TFs from GWAS SNPs.

Date: 2020
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DOI: 10.1038/s41467-020-16106-x

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