title: Chromatin proteomic profiling reveals novel proteins associated with histone-marked genomic regions.
abstract: More than a thousand proteins are thought to contribute to mammalian chromatin and its regulation, but our understanding of the genomic occupancy and function of most of these proteins is limited. Here we describe an approach, which we call "chromatin proteomic profiling," to identify proteins associated with genomic regions marked by specifically modified histones. We used ChIP-MS to identify proteins associated with genomic regions marked by histones modified at specific lysine residues, including H3K27ac, H3K4me3, H3K79me2, H3K36me3, H3K9me3, and H4K20me3, in ES cells. We identified 332 known and 114 novel proteins associated with these histone-marked genomic segments. Many of the novel candidates have been implicated in various diseases, and their chromatin association may provide clues to disease mechanisms. More than 100 histone modifications have been described, so similar chromatin proteomic profiling studies should prove to be valuable for identifying many additional chromatin-associated proteins in a broad spectrum of cell types.
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, MA 02142;
authors.forename: Xiong
authors.initials: X
authors.lastname: Ji
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, MA 02142; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139;
authors.forename: Daniel B
authors.initials: DB
authors.lastname: Dadon
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, MA 02142;
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Abraham
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, MA 02142;
authors.forename: Tong Ihn
authors.initials: TI
authors.lastname: Lee
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, MA 02142; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139;
authors.forename: Rudolf
authors.initials: R
authors.lastname: Jaenisch
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115; and Department of Medicine, Harvard Medical School, Boston, MA 02115.
authors.forename: James E
authors.initials: JE
authors.lastname: Bradner
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, MA 02142; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139; young@wi.mit.edu.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Young
mesh_terms: D000818:Animals; D002843:Chromatin / Q000737:chemistry*; D047369:Chromatin Immunoprecipitation; D003432:Cross-Linking Reagents / Q000737:chemistry; D053595:Embryonic Stem Cells / Q000166:cytology; D005347:Fibroblasts / Q000378:metabolism; D020869:Gene Expression Profiling; D016678:Genome; D023281:Genomics; D006657:Histones / Q000737:chemistry*; D006801:Humans; D008239:Lysine / Q000737:chemistry; D013058:Mass Spectrometry; D051379:Mice; D008810:Mice, Inbred C57BL; D020543:Proteome; D040901:Proteomics / Q000379:methods*; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D002843:Chromatin; D003432:Cross-Linking Reagents; D006657:Histones; D020543:Proteome; D014157:Transcription Factors; D008239:Lysine
keywords: chromatin; genomics; proteomics