1Charles Perkins Centre and School of Mathematics and Statistics, University of Sydney, Camperdown, NSW 2006, Australia2Systems Biology Group, Epigenetics & Stem Cell Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, RTP, NC 27709, USA3Institute of Human Genetics, CNRS UPR 1142, Montpellier, France4Victor Chang Cardiac Research Institute5St. Vincent's Clinical School, University of New South Wales, Darlinghurst, NSW 2010, Australia
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Motivation:DNA binding proteins such as chromatin remodellers, transcription factors (TFs), histone modifiers and co-factors often bind cooperatively to activate or repress their target genes in a cell type-specific manner. Nonetheless, the precise role of cooperative binding in defining cell-type identity is still largely uncharacterized.Results:Here, we collected and analyzed 214 public datasets representing chromatin immunoprecipitation followed by sequencing (ChIP-Seq) of 104 DNA binding proteins in embryonic stem cell (ESC) lines. We classified their binding sites into those proximal to gene promoters and those in distal regions, and developed a web resource called Proximal And Distal (PAD) clustering to identify their co-localization at these respective regions. Using this extensive dataset, we discovered an extensive co-localization of BRG1 and CHD7 at distal but not proximal regions. The comparison of co-localization sites to those bound by either BRG1 or CHD7 alone showed an enrichment of ESC master TFs binding and active chromatin architecture at co-localization sites. Most notably, our analysis reveals the co-dependency of BRG1 and CHD7 at distal regions on regulating expression of their common target genes in ESC. This work sheds light on cooperative binding of TF binding proteins in regulating gene expression in ESC, and demonstrates the utility of integrative analysis of a manually curated compendium of genome-wide protein binding profiles in our online resource PAD.Availability and Implementation:PAD is freely available at http://pad.victorchang.edu.au/ and its source code is available via an open source GPL 3.0 license at https://github.com/VCCRI/PAD/Contact:email@example.com or firstname.lastname@example.orgSupplementary information:Supplementary data are available at Bioinformatics online.