title: Epigenome analyses using BAC microarrays identify evolutionary conservation of tissue-specific methylation of SHANK3.
abstract: CpG islands are present in one-half of all human and mouse genes and typically overlap with promoters or exons. We developed a method for high-resolution analysis of the methylation status of CpG islands genome-wide, using arrays of BAC clones and the methylation-sensitive restriction enzyme NotI. Here we demonstrate the accuracy and specificity of the method. By computationally mapping all NotI sites, methylation events can be defined with single-nucleotide precision throughout the genome. We also demonstrate the unique expandability of the array method using a different methylation-sensitive restriction enzyme, BssHII. We identified and validated new CpG island loci that are methylated in a tissue-specific manner in normal human tissues. The methylation status of the CpG islands is associated with gene expression for several genes, including SHANK3, which encodes a structural protein in neuronal postsynaptic densities. Defects in SHANK3 seem to underlie human 22q13 deletion syndrome. Furthermore, these patterns for SHANK3 are conserved in mice and rats.
authors.affiliation: The Brain Tumor Research Center, Department of Neurological Surgery and the Biomedical Sciences Program, University of California San Francisco, San Franciso, California 94143, USA.
authors.forename: Tsui-Ting
authors.initials: TT
authors.lastname: Ching
authors.forename: Alika K
authors.initials: AK
authors.lastname: Maunakea
authors.forename: Peter
authors.initials: P
authors.lastname: Jun
authors.forename: Chibo
authors.initials: C
authors.lastname: Hong
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Zardo
authors.forename: Daniel
authors.initials: D
authors.lastname: Pinkel
authors.forename: Donna G
authors.initials: DG
authors.lastname: Albertson
authors.forename: Jane
authors.initials: J
authors.lastname: Fridlyand
authors.forename: Jian-Hua
authors.initials: JH
authors.lastname: Mao
authors.forename: Ksenya
authors.initials: K
authors.lastname: Shchors
authors.forename: William A
authors.initials: WA
authors.lastname: Weiss
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Costello
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D022202:Chromosomes, Artificial, Bacterial; D017124:Conserved Sequence; D018899:CpG Islands; D019175:DNA Methylation; D015252:Deoxyribonucleases, Type II Site-Specific; D006801:Humans; D051379:Mice; D009419:Nerve Tissue Proteins; D020411:Oligonucleotide Array Sequence Analysis; D009928:Organ Specificity; D012045:Regulatory Sequences, Nucleic Acid; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D002352:Carrier Proteins; D009419:Nerve Tissue Proteins; C492357:SHANK3 protein, human; C044171:endodeoxyribonuclease BSSHII; D015252:Deoxyribonucleases, Type II Site-Specific; C038565:GCGGCCGC-specific type II deoxyribonucleases