title: Elucidating Combinatorial Chromatin States at Single-Nucleosome Resolution.
abstract: Chromatin immunoprecipitation followed by sequencing (ChIP-seq) has been instrumental to our current view of chromatin structure and function. It allows genome-wide mapping of histone marks, which demarcate biologically relevant domains. However, ChIP-seq is an ensemble measurement reporting the average occupancy of individual marks in a cell population. Consequently, our understanding of the combinatorial nature of chromatin states relies almost exclusively on correlation between the genomic distributions of individual marks. Here, we report the development of combinatorial-iChIP to determine the genome-wide co-occurrence of histone marks at single-nucleosome resolution. By comparing to a null model, we show that certain combinations of overlapping marks (H3K36me3 and H3K79me3) co-occur more frequently than would be expected by chance, while others (H3K4me3 and H3K36me3) do not, reflecting differences in the underlying chromatin pathways. We further use combinatorial-iChIP to illuminate aspects of the Set2-RPD3S pathway. This approach promises to improve our understanding of the combinatorial complexity of chromatin.
authors: School of Computer Science and Engineering and Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem 9190401, Israel. Electronic address: ronensadeh@gmail.com.
authors: Ronen
authors: R
authors: Sadeh
authors: School of Computer Science and Engineering and Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem 9190401, Israel.
authors: Roee
authors: R
authors: Launer-Wachs
authors: School of Computer Science and Engineering and Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem 9190401, Israel.
authors: Hava
authors: H
authors: Wandel
authors: School of Computer Science and Engineering and Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem 9190401, Israel.
authors: Ayelet
authors: A
authors: Rahat
authors: School of Computer Science and Engineering and Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem 9190401, Israel; Broad Institute of MIT and Harvard, Cambridge, MA 02139, USA. Electronic address: nir@cs.huji.ac.il.
authors: Nir
authors: N
authors: Friedman
mesh_terms: D047369:Chromatin Immunoprecipitation / Q000379:methods; D002874:Chromosome Mapping; D015966:Gene Expression Regulation, Fungal; D016681:Genome, Fungal; D059014:High-Throughput Nucleotide Sequencing; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism; D006657:Histones / Q000235:genetics* / Q000378:metabolism; D008745:Methylation; D008780:Methyltransferases / Q000235:genetics / Q000378:metabolism; D009707:Nucleosomes / Q000737:chemistry* / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D006657:Histones; D009707:Nucleosomes; D029701:Saccharomyces cerevisiae Proteins; D008780:Methyltransferases; C448996:Set2 protein, S cerevisiae; C071665:RPD3 protein, S cerevisiae; D006655:Histone Deacetylases
keywords: ChIP; Rpd3; Set2; chromatin; histone modifications; nucleosomes