title: Combinatorial patterning of chromatin regulators uncovered by genome-wide location analysis in human cells.
abstract: Hundreds of chromatin regulators (CRs) control chromatin structure and function by catalyzing and binding histone modifications, yet the rules governing these key processes remain obscure. Here, we present a systematic approach to infer CR function. We developed ChIP-string, a meso-scale assay that combines chromatin immunoprecipitation with a signature readout of 487 representative loci. We applied ChIP-string to screen 145 antibodies, thereby identifying effective reagents, which we used to map the genome-wide binding of 29 CRs in two cell types. We found that specific combinations of CRs colocalize in characteristic patterns at distinct chromatin environments, at genes of coherent functions, and at distal regulatory elements. When comparing between cell types, CRs redistribute to different loci but maintain their modular and combinatorial associations. Our work provides a multiplex method that substantially enhances the ability to monitor CR binding, presents a large resource of CR maps, and reveals common principles for combinatorial CR function.
authors.affiliation: Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
authors.forename: Oren
authors.initials: O
authors.lastname: Ram
authors.forename: Alon
authors.initials: A
authors.lastname: Goren
authors.forename: Ido
authors.initials: I
authors.lastname: Amit
authors.forename: Noam
authors.initials: N
authors.lastname: Shoresh
authors.forename: Nir
authors.initials: N
authors.lastname: Yosef
authors.forename: Jason
authors.initials: J
authors.lastname: Ernst
authors.forename: Manolis
authors.initials: M
authors.lastname: Kellis
authors.forename: Melissa
authors.initials: M
authors.lastname: Gymrek
authors.forename: Robbyn
authors.initials: R
authors.lastname: Issner
authors.forename: Michael
authors.initials: M
authors.lastname: Coyne
authors.forename: Timothy
authors.initials: T
authors.lastname: Durham
authors.forename: Xiaolan
authors.initials: X
authors.lastname: Zhang
authors.forename: Julie
authors.initials: J
authors.lastname: Donaghey
authors.forename: Charles B
authors.initials: CB
authors.lastname: Epstein
authors.forename: Aviv
authors.initials: A
authors.lastname: Regev
authors.forename: Bradley E
authors.initials: BE
authors.lastname: Bernstein
mesh_terms: D002843:Chromatin / Q000737:chemistry / Q000378:metabolism*; D042002:Chromatin Assembly and Disassembly; D047369:Chromatin Immunoprecipitation / Q000379:methods*; D053595:Embryonic Stem Cells; D016678:Genome; D023281:Genomics / Q000379:methods*; D042421:Histone Code; D006801:Humans; D020014:K562 Cells
chemical_list: D002843:Chromatin