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.
Highlights
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
We systematically model the genomic distance over which TFs regulate genes, and evaluate how these regulatory ranges depend on TFs and on genomic and chromatin contexts
A TF-binding site’s regulatory effects on a gene’s expression level typically diminishes monotonically with the genomic distance separating the TF-binding site and the gene transcription start site (TSS). This assumption is motivated by the genomic distance-dependent monotonic decay observed in chromatin interaction experiments[11], eQTL studies showing that single-nucleotide polymorphisms (SNPs) associating with the gene expression
Summary
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. We systematically model the genomic distance over which TFs regulate genes, and evaluate how these regulatory ranges depend on TFs and on genomic and chromatin contexts (measured by H3K27ac ChIP-seq[7]). Our integrative analyses of large compendia of ChIP-seq[3], gene expression[8,9], and eQTL9 data reveal a previously undescribed relationship between TF regulatory ranges and local genomic and chromatin contexts. These results suggest the existence of two distinct ‘short-range’ and ‘long-range’ classes of TF with contrasting characteristics, including genome-wide binding, auto-regulatory, tissue-restricted expression, and pioneer-factor like properties. Unlike previous studies, which mostly focus on individual TFs, our findings illustrate commonalities between TFs and provided a succinct framework for interpreting complex gene regulation
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
