title: Sequence features accurately predict genome-wide MeCP2 binding in vivo.
abstract: Methyl-CpG binding protein 2 (MeCP2) is critical for proper brain development and expressed at near-histone levels in neurons, but the mechanism of its genomic localization remains poorly understood. Using high-resolution MeCP2-binding data, we show that DNA sequence features alone can predict binding with 88% accuracy. Integrating MeCP2 binding and DNA methylation in a probabilistic graphical model, we demonstrate that previously reported genome-wide association with methylation is in part due to MeCP2's affinity to GC-rich chromatin, a result replicated using published data. Furthermore, MeCP2 co-localizes with nucleosomes. Finally, MeCP2 binding downstream of promoters correlates with increased expression in Mecp2-deficient neurons.
authors.affiliation: Carl R. Woese Institute for Genomic Biology, University of Illinois, Urbana-Champaign, Champaign, Illinois 61801, USA.|Department of Physics, University of Illinois, Urbana-Champaign, Champaign, Illinois 61801, USA.|Department of Biological Sciences, Columbia University, New York, New York 10027, USA.
authors.forename: H Tomas
authors.initials: HT
authors.lastname: Rube
authors.affiliation: Department of Cell Biology and Human Anatomy, University of California School of Medicine, Davis, California 95616, USA.|Division of Life Sciences, Korea University, Seoul 136-713, Korea.
authors.forename: Wooje
authors.initials: W
authors.lastname: Lee
authors.affiliation: Carl R. Woese Institute for Genomic Biology, University of Illinois, Urbana-Champaign, Champaign, Illinois 61801, USA.|Department of Physics, University of Illinois, Urbana-Champaign, Champaign, Illinois 61801, USA.
authors.forename: Miroslav
authors.initials: M
authors.lastname: Hejna
authors.affiliation: Department of Cell Biology and Human Anatomy, University of California School of Medicine, Davis, California 95616, USA.
authors.forename: Huaiyang
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Medical Microbiology and Immunology, Genome Center, MIND Institute, University of California School of Medicine, Davis, California 95616, USA.
authors.forename: Dag H
authors.initials: DH
authors.lastname: Yasui
authors.affiliation: Department of Cell Biology and Human Anatomy, University of California School of Medicine, Davis, California 95616, USA.
authors.forename: John F
authors.initials: JF
authors.lastname: Hess
authors.affiliation: Department of Medical Microbiology and Immunology, Genome Center, MIND Institute, University of California School of Medicine, Davis, California 95616, USA.
authors.forename: Janine M
authors.initials: JM
authors.lastname: LaSalle
authors.affiliation: Carl R. Woese Institute for Genomic Biology, University of Illinois, Urbana-Champaign, Champaign, Illinois 61801, USA.|Department of Physics, University of Illinois, Urbana-Champaign, Champaign, Illinois 61801, USA.|Department of Bioengineering, University of Illinois, Urbana-Champaign, Champaign, Illinois 61801, USA.|Department of Biostatistics and Epidemiology, University of California, San Francisco, California 94158, USA.
authors.forename: Jun S
authors.initials: JS
authors.lastname: Song
authors.affiliation: Department of Cell Biology and Human Anatomy, University of California School of Medicine, Davis, California 95616, USA.
authors.forename: Qizhi
authors.initials: Q
authors.lastname: Gong
mesh_terms: D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002843:Chromatin / Q000378:metabolism*; D047369:Chromatin Immunoprecipitation; D019175:DNA Methylation / Q000235:genetics*; D020862:GC Rich Sequence; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D009474:Neurons; D009707:Nucleosomes / Q000378:metabolism; D009831:Olfactory Mucosa / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D017422:Sequence Analysis, DNA; D017423:Sequence Analysis, RNA
chemical_list: D002843:Chromatin; C497393:Mecp2 protein, mouse; D051783:Methyl-CpG-Binding Protein 2; D009707:Nucleosomes