title: DNA methylation regulates tissue-specific expression of Shank3.
abstract: Tissue-specific gene expression can be controlled by epigenetic modifications such as DNA methylation. SHANK3, together with its homologues SHANK1 and SHANK2, has a central functional and structural role in excitatory synapses and is involved in the human chromosome 22q13 deletion syndrome. In this report, we show by DNA methylation analysis in lymphocytes, brain cortex, cerebellum and heart that the three SHANK genes possess several methylated CpG boxes, but only SHANK3 CpG islands are highly methylated in tissues where protein expression is low or absent and unmethylated where expression is present. SHANK3 protein expression is significantly reduced in hippocampal neurons after treatment with methionine, while HeLa cells become able to express SHANK3 after treatment with 5-Aza-2'-deoxycytidine. Altogether, these data suggest the existence of a specific epigenetic control mechanism regulating SHANK3, but not SHANK1 and SHANK2, expression.
authors.affiliation: E. Medea Scientific Institute, Bosisio Parini, LC, Italy.
authors.forename: Silvana
authors.initials: S
authors.lastname: Beri
authors.forename: Noemi
authors.initials: N
authors.lastname: Tonna
authors.forename: Giorgia
authors.initials: G
authors.lastname: Menozzi
authors.forename: Maria Clara
authors.initials: MC
authors.lastname: Bonaglia
authors.forename: Carlo
authors.initials: C
authors.lastname: Sala
authors.forename: Roberto
authors.initials: R
authors.lastname: Giorda
mesh_terms: D000818:Animals; D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D001921:Brain / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D002478:Cells, Cultured; D018899:CpG Islands / Q000187:drug effects / Q000502:physiology; D019175:DNA Methylation / Q000187:drug effects; D000077209:Decitabine; D004622:Embryo, Mammalian; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015870:Gene Expression; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006321:Heart / Q000502:physiology; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism; D008715:Methionine / Q000494:pharmacology; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D051381:Rats; D014018:Tissue Distribution / Q000187:drug effects / Q000502:physiology; D014162:Transfection
chemical_list: D002352:Carrier Proteins; D004791:Enzyme Inhibitors; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; D034741:RNA, Small Interfering; C492356:Shank3 protein, mouse; D049452:Green Fluorescent Proteins; D000077209:Decitabine; D008715:Methionine; D001374:Azacitidine