DNA Methylation Regulates Tissue-Specific Expression of Shank3

J Neurochem. 2007 Jun;101(5):1380-91. doi: 10.1111/j.1471-4159.2007.04539.x. Epub 2007 Apr 10.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Azacitidine / analogs & derivatives
  • Azacitidine / pharmacology
  • Brain / metabolism
  • Carrier Proteins / metabolism*
  • Cells, Cultured
  • CpG Islands / drug effects
  • CpG Islands / physiology
  • DNA Methylation* / drug effects
  • Decitabine
  • Embryo, Mammalian
  • Enzyme Inhibitors / pharmacology
  • Gene Expression
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / physiology*
  • Gene Expression Regulation, Neoplastic
  • Green Fluorescent Proteins / metabolism
  • Heart / physiology
  • Hippocampus / cytology
  • Humans
  • Lymphocytes / metabolism
  • Methionine / pharmacology
  • Nerve Tissue Proteins
  • Neurons / cytology
  • Neurons / metabolism
  • RNA, Small Interfering / pharmacology
  • Rats
  • Tissue Distribution / drug effects
  • Tissue Distribution / physiology
  • Transfection

Substances

  • Carrier Proteins
  • Enzyme Inhibitors
  • Nerve Tissue Proteins
  • RNA, Small Interfering
  • Shank3 protein, mouse
  • Green Fluorescent Proteins
  • Decitabine
  • Methionine
  • Azacitidine