Co-ChIP enables genome-wide mapping of histone mark co-occurrence at single-molecule resolution

Assaf Weiner, David Lara-Astiaso, Vladislav Krupalnik, Ohad Gafni, Eyal David, Deborah R. Winter, Jacob H. Hanna, Ido Amit

Research output: Contribution to journalArticlepeer-review

63 Scopus citations


Histone modifications play an important role in chromatin organization and transcriptional regulation, but despite the large amount of genome-wide histone modification data collected in different cells and tissues, little is known about co-occurrence of modifications on the same nucleosome. Here we present a genome-wide quantitative method for combinatorial indexed chromatin immunoprecipitation (co-ChIP) to characterize co-occurrence of histone modifications on nucleosomes. Using co-ChIP, we study the genome-wide co-occurrence of 14 chromatin marks (70 pairwise combinations), and find previously undescribed co-occurrence patterns, including the co-occurrence of H3K9me1 and H3K27ac in super-enhancers. Finally, we apply co-ChIP to measure the distribution of the bivalent H3K4me3-H3K27me3 domains in two distinct mouse embryonic stem cell (mESC) states and in four adult tissues. We observe dynamic changes in 5,786 regions and discover both loss and de novo gain of bivalency in key tissue-specific regulatory genes, suggesting a functional role for bivalent domains during different stages of development. These results show that co-ChIP can reveal the complex interactions between histone modifications.

Original languageEnglish (US)
Pages (from-to)953-961
Number of pages9
JournalNature biotechnology
Issue number9
StatePublished - Sep 1 2016

Bibliographical note

Funding Information:
ACKNOWLEDGMENTS: We thank G. Brodsky for art work. I.A. is supported by the European Research Council (309788), the Israel Science foundation (782/11) and the BLUEPRINT FP7 consortium, the Ernest and Bonnie Beutler Research Program of Excellence in Genomic Medicine, a Minerva Stiftung research grant, and the National Human Genome Research Institute Center for Excellence in Genome Science (1P50HG006193), the Israeli Ministry of Science, Technology and Space, the David and Fela Shapell Family Foundation, and the Abramson Family Center for Young Scientists. I.A. is the incumbent of the Alan and Laraine Fischer Career Development Chair. ChIP-Seq and co-ChIP data are deposited in Gene Expression Omnibus, accession number GSE83833.

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© 2016 Nature America, Inc. All rights reserved.

Copyright 2017 Elsevier B.V., All rights reserved.


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