title: Systematic identification of protein combinations mediating chromatin looping.
abstract: Chromatin looping plays a pivotal role in gene expression and other biological processes through bringing distal regulatory elements into spatial proximity. The formation of chromatin loops is mainly mediated by DNA-binding proteins (DBPs) that bind to the interacting sites and form complexes in three-dimensional (3D) space. Previously, identification of DBP cooperation has been limited to those binding to neighbouring regions in the proximal linear genome (1D cooperation). Here we present the first study that integrates protein ChIP-seq and Hi-C data to systematically identify both the 1D- and 3D-cooperation between DBPs. We develop a new network model that allows identification of cooperation between multiple DBPs and reveals cell-type-specific and -independent regulations. Using this framework, we retrieve many known and previously unknown 3D-cooperations between DBPs in chromosomal loops that may be a key factor in influencing the 3D organization of chromatin.
authors.affiliation: Graduate Program in Bioinformatics and Systems Biology, University of California, La Jolla, San Diego, California 92093-0359, USA.
authors.forename: Kai
authors.identifier: http://orcid.org/0000-0003-3454-7357
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Department of Chemistry and Biochemistry, University of California, La Jolla, San Diego, California 92093-0359, USA.|Department of Cellular and Molecular Medicine, University of California, La Jolla, San Diego, California 92093-0359, USA.
authors.forename: Nan
authors.identifier: http://orcid.org/0000-0001-7826-4688
authors.initials: N
authors.lastname: Li
authors.affiliation: Department of Chemistry and Biochemistry, University of California, La Jolla, San Diego, California 92093-0359, USA.|Department of Cellular and Molecular Medicine, University of California, La Jolla, San Diego, California 92093-0359, USA.
authors.forename: Richard I
authors.initials: RI
authors.lastname: Ainsworth
authors.affiliation: Graduate Program in Bioinformatics and Systems Biology, University of California, La Jolla, San Diego, California 92093-0359, USA.|Department of Chemistry and Biochemistry, University of California, La Jolla, San Diego, California 92093-0359, USA.|Department of Cellular and Molecular Medicine, University of California, La Jolla, San Diego, California 92093-0359, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
mesh_terms: D001483:Base Sequence; D002843:Chromatin / Q000737:chemistry* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D053263:Gene Regulatory Networks; D006801:Humans; D020014:K562 Cells; D008954:Models, Biological; D016011:Normal Distribution; D009690:Nucleic Acid Conformation; D011485:Protein Binding
chemical_list: D002843:Chromatin; D004268:DNA-Binding Proteins