title: Co-ChIP enables genome-wide mapping of histone mark co-occurrence at single-molecule resolution.
abstract: 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.
authors.affiliation: The Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Assaf
authors.initials: A
authors.lastname: Weiner
authors.affiliation: The Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: David
authors.initials: D
authors.lastname: Lara-Astiaso
authors.affiliation: The Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Vladislav
authors.initials: V
authors.lastname: Krupalnik
authors.affiliation: The Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Ohad
authors.initials: O
authors.lastname: Gafni
authors.affiliation: The Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Eyal
authors.initials: E
authors.lastname: David
authors.affiliation: The Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Deborah R
authors.initials: DR
authors.lastname: Winter
authors.affiliation: The Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Jacob H
authors.identifier: 0000-0003-2042-9974
authors.initials: JH
authors.lastname: Hanna
authors.affiliation: The Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Ido
authors.initials: I
authors.lastname: Amit
mesh_terms: D000818:Animals; D001665:Binding Sites; D047369:Chromatin Immunoprecipitation / Q000379:methods*; D002874:Chromosome Mapping / Q000379:methods*; D020650:Combinatorial Chemistry Techniques / Q000379:methods; D016678:Genome / Q000235:genetics*; D059014:High-Throughput Nucleotide Sequencing; D042421:Histone Code / Q000235:genetics*; D006657:Histones / Q000235:genetics*; D051379:Mice; D008832:Microchemistry / Q000379:methods*; D011485:Protein Binding; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D006657:Histones