Combinatorial Patterning of Chromatin Regulators Uncovered by Genome-wide Location Analysis in Human Cells

Overview

Journal Cell

Publisher Cell Press

Specialty Cell Biology

Date 2011 Dec 27

PMID 22196736

Citations 211

Authors

Oren Ram

Alon Goren

Ido Amit

Noam Shoresh

Nir Yosef

Jason Ernst

Manolis Kellis

Melissa Gymrek

Robbyn Issner

Michael Coyne

Timothy Durham

Xiaolan Zhang

Julie Donaghey

Charles B Epstein

Aviv Regev

Bradley E Bernstein

Affiliations

Soon will be listed here.

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.

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