title: Targeted Histone Peptides: Insights into the Spatial Regulation of the Methyltransferase PRC2 by using a Surrogate of Heterotypic Chromatin.
abstract: Eukaryotic genomes are dynamically regulated through a host of epigenetic stimuli. The substrate for these epigenetic transactions, chromatin, is a polymer of nucleosome building blocks. In native chromatin, each nucleosome can differ from its neighbors as a result of covalent modifications to both the DNA and the histone packaging proteins. The heterotypic nature of chromatin presents a formidable obstacle to biochemical studies seeking to understand the role of context on epigenetic regulation. A chemical approach to the production of heterotypic chromatin that can be used in such studies is introduced. This method involves the attachment of a user-defined modified histone peptide to a designated nucleosome within the polymer by using a peptide nucleic acid (PNA) targeting compound. This strategy was applied to dissect the effect of chromatin context on the activity of the histone methyltransferase PRC2. The results show that PRC2 can be stimulated to produce histone H3 methylation from a defined nucleation site.
authors: Department of Chemistry, Princeton University, Princeton, NJ 08544 (USA).
authors: Zachary Z
authors: ZZ
authors: Brown
authors: Department of Chemistry, Princeton University, Princeton, NJ 08544 (USA).
authors: Manuel M
authors: MM
authors: Müller
authors: Department of Chemistry, Princeton University, Princeton, NJ 08544 (USA).|Present address: School of Medicine, Emory University, Atlanta, GA 30322 (USA).
authors: Ha Eun
authors: HE
authors: Kong
authors: Wisconsin Institute for Discovery, University of Wisconsin, Madison, WI 53715 (USA).
authors: Peter W
authors: PW
authors: Lewis
authors: Department of Chemistry, Princeton University, Princeton, NJ 08544 (USA). muir@princeton.edu.
authors: Tom W
authors: TW
authors: Muir
mesh_terms: D002843:Chromatin / Q000378:metabolism*; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D057890:Epigenomics; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase / Q000737:chemistry / Q000378:metabolism*; D006657:Histones / Q000737:chemistry / Q000378:metabolism*; D008745:Methylation; D020135:Peptide Nucleic Acids / Q000737:chemistry / Q000378:metabolism; D010455:Peptides / Q000737:chemistry / Q000378:metabolism
chemical_list: D002843:Chromatin; D006657:Histones; D020135:Peptide Nucleic Acids; D010455:Peptides; D004247:DNA; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase
keywords: chromatin; epigenetics; histones; peptide nucleic acids; peptides