title: An interspecies analysis reveals a key role for unmethylated CpG dinucleotides in vertebrate Polycomb complex recruitment.
abstract: The role of DNA sequence in determining chromatin state is incompletely understood. We have previously demonstrated that large chromosomal segments from human cells recapitulate their native chromatin state in mouse cells, but the relative contribution of local sequences versus their genomic context remains unknown. In this study, we compare orthologous chromosomal regions for which the human locus establishes prominent sites of Polycomb complex recruitment in pluripotent stem cells, whereas the corresponding mouse locus does not. Using recombination-mediated cassette exchange at the mouse locus, we establish the primacy of local sequences in the encoding of chromatin state. We show that the signal for chromatin bivalency is redundantly encoded across a bivalent domain and that this reflects competition between Polycomb complex recruitment and transcriptional activation. Furthermore, our results suggest that a high density of unmethylated CpG dinucleotides is sufficient for vertebrate Polycomb recruitment. This model is supported by analysis of DNA methyltransferase-deficient embryonic stem cells.
authors: MRC Haematology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
authors: Magnus D
authors: MD
authors: Lynch
authors: Andrew J H
authors: AJ
authors: Smith
authors: Marco
authors: M
authors: De Gobbi
authors: Maria
authors: M
authors: Flenley
authors: Jim R
authors: JR
authors: Hughes
authors: Douglas
authors: D
authors: Vernimmen
authors: Helena
authors: H
authors: Ayyub
authors: Jacqueline A
authors: JA
authors: Sharpe
authors: Jacqueline A
authors: JA
authors: Sloane-Stanley
authors: Linda
authors: L
authors: Sutherland
authors: Stephen
authors: S
authors: Meek
authors: Tom
authors: T
authors: Burdon
authors: Richard J
authors: RJ
authors: Gibbons
authors: David
authors: D
authors: Garrick
authors: Douglas R
authors: DR
authors: Higgs
mesh_terms: D000818:Animals; D002478:Cells, Cultured / Q000378:metabolism; D002843:Chromatin / Q000235:genetics; D002874:Chromosome Mapping; D002885:Chromosomes, Human, Pair 16; D018899:CpG Islands / Q000502:physiology*; D019175:DNA Methylation; D004274:DNA, Recombinant / Q000235:genetics; D053595:Embryonic Stem Cells / Q000378:metabolism; D005786:Gene Expression Regulation / Q000235:genetics*; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D039904:Pluripotent Stem Cells / Q000378:metabolism; D063146:Polycomb-Group Proteins; D011995:Recombination, Genetic; D012045:Regulatory Sequences, Nucleic Acid; D012097:Repressor Proteins / Q000378:metabolism*; D013045:Species Specificity; D014158:Transcription, Genetic; D055542:alpha-Globins / Q000235:genetics*
chemical_list: D002843:Chromatin; D004274:DNA, Recombinant; D063146:Polycomb-Group Proteins; D012097:Repressor Proteins; D055542:alpha-Globins