You are here

Cell DOI:10.1016/j.cell.2011.09.057

Combinatorial patterning of chromatin regulators uncovered by genome-wide location analysis in human cells.

Publication TypeJournal Article
Year of Publication2011
AuthorsRam, O, Goren, A, Amit, I, Shoresh, N, Yosef, N, Ernst, J, Kellis, M, Gymrek, M, Issner, R, Coyne, M, Durham, T, Zhang, X, Donaghey, J, Epstein, CB, Regev, A, Bernstein, BE
Date Published2011 Dec 23
KeywordsChromatin, Chromatin Assembly and Disassembly, Chromatin Immunoprecipitation, Embryonic Stem Cells, Genome, Genomics, Histone Code, Humans, K562 Cells

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.


Alternate JournalCell
PubMed ID22196736
PubMed Central IDPMC3312319
Grant ListR01 HG004037 / HG / NHGRI NIH HHS / United States
U54 HG004570-02 / HG / NHGRI NIH HHS / United States
U54 HG004570-03S1 / HG / NHGRI NIH HHS / United States
DP1 CA174427 / CA / NCI NIH HHS / United States
U54 HG004570-01 / HG / NHGRI NIH HHS / United States
U54 HG004570-04 / HG / NHGRI NIH HHS / United States
U54 HG004570 / HG / NHGRI NIH HHS / United States
/ / Howard Hughes Medical Institute / United States
U54 HG004570-03 / HG / NHGRI NIH HHS / United States