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

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• 作者：Oren Ram¹ ; ² ; ³ ; ⁴ ; ⁷ ; Alon Goren¹ ; ² ; ³ ; ⁴ ; ⁷ ; Ido Amit¹ ; ² ; Noam Shoresh¹ ; Nir Yosef¹ ; ² ; Jason Ernst¹ ; ⁵ ; Manolis Kellis¹ ; ⁵ ; Melissa Gymrek¹ ; ² ; ³ ; ⁴ ; Robbyn Issner¹ ; Michael Coyne¹ ; Timothy Durham¹ ; Xiaolan Zhang¹ ; Julie Donaghey¹ ; Charles  ; B. Epstein¹ ; Aviv Regev¹ ; ² ; ⁶ ; ^{aregev@broad.mit.edu} ; Bradley  ; E. Bernstein¹ ; ² ; ³ ; ⁴ ; ^{bernstein.bradley@mgh.harvard.edu}
• 刊名：Cell
• 出版年：2011
• 出版时间：23 December 2011
• 年：2011
• 卷：147
• 期：7
• 页码：1628-1639
• 全文大小：1520 K

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Summary

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.