DNA methylation regulates tissue-specific expression of Shank3.
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.
Beri
Silvana
S
E. Medea Scientific Institute, Bosisio Parini, LC, Italy.
Tonna
Noemi
N
Menozzi
Giorgia
G
Bonaglia
Maria Clara
MC
Sala
Carlo
C
Giorda
Roberto
R
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
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