title: Synthetic CpG islands reveal DNA sequence determinants of chromatin structure.
abstract: The mammalian genome is punctuated by CpG islands (CGIs), which differ sharply from the bulk genome by being rich in G + C and the dinucleotide CpG. CGIs often include transcription initiation sites and display 'active' histone marks, notably histone H3 lysine 4 methylation. In embryonic stem cells (ESCs) some CGIs adopt a 'bivalent' chromatin state bearing simultaneous 'active' and 'inactive' chromatin marks. To determine whether CGI chromatin is developmentally programmed at specific genes or is imposed by shared features of CGI DNA, we integrated artificial CGI-like DNA sequences into the ESC genome. We found that bivalency is the default chromatin structure for CpG-rich, G + C-rich DNA. A high CpG density alone is not sufficient for this effect, as A + T-rich sequence settings invariably provoke de novo DNA methylation leading to loss of CGI signature chromatin. We conclude that both CpG-richness and G + C-richness are required for induction of signature chromatin structures at CGIs.
authors.affiliation: The Wellcome Trust Centre for Cell Biology, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Wachter
authors.affiliation: The Wellcome Trust Centre for Cell Biology, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Timo
authors.initials: T
authors.lastname: Quante
authors.affiliation: The Wellcome Trust Centre for Cell Biology, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Cara
authors.initials: C
authors.lastname: Merusi
authors.affiliation: The Wellcome Trust Centre for Cell Biology, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Arczewska
authors.affiliation: Genomics and Biotechnology Centre, Technische Universitaet Dresden, Dresden, Germany.
authors.forename: Francis
authors.initials: F
authors.lastname: Stewart
authors.affiliation: The Wellcome Trust Centre for Cell Biology, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Shaun
authors.initials: S
authors.lastname: Webb
authors.affiliation: The Wellcome Trust Centre for Cell Biology, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Adrian
authors.initials: A
authors.lastname: Bird
mesh_terms: D020856:AT Rich Sequence / Q000235:genetics; D000818:Animals; D001482:Base Composition / Q000235:genetics; D001483:Base Sequence; D002460:Cell Line; D002843:Chromatin / Q000737:chemistry*; D018899:CpG Islands / Q000235:genetics*; D019175:DNA Methylation; D053595:Embryonic Stem Cells / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D008239:Lysine / Q000378:metabolism; D051379:Mice; D011401:Promoter Regions, Genetic; D012319:RNA Polymerase II / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism
chemical_list: D002843:Chromatin; C501971:Cxxc1 protein, mouse; D006657:Histones; D015534:Trans-Activators; D012319:RNA Polymerase II; D008239:Lysine
keywords: CpG islands; DNA methylation; bivalent chromatin; chromosomes; genes; histone modifications; mouse