Allele C-specific methylation of the 5-HT2A receptor gene: evidence for correlation with its expression and expression of DNA methylase DNMT1

J Neurosci Res. 2006 Feb 15;83(3):362-73. doi: 10.1002/jnr.20732.


Differential DNA methylation has been suggested to contribute to differential activity of alleles C and T and thereby to genetic associations between the C/T(102) polymorphism in the 5-HT2A receptor gene (5HT2AR) and psychiatric disorders. We surveyed methylation in two CpG sites, which are specific to allele C. The majority of allele C-specific CpG sites were methylated in human temporal cortex and peripheral leukocytes and levels of methylation varied between individuals. Levels of methylation in the promoter correlated significantly with the expression of 5HT2AR. Methylation of allele C-specific CpG sites in the first exon correlated significantly with the expression of DNA methylase 1 (DNMT1) but not S-adenosylhomocysteine hydrolase (AHCY). These findings support the hypothesis that allele-specific DNA methylation is involved in regulation of 5HT2AR expression, influencing expression differences between alleles C and T.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Intramural

MeSH terms

  • Adult
  • Alleles*
  • Analysis of Variance
  • Base Sequence
  • Brain / metabolism*
  • CpG Islands / physiology
  • DNA (Cytosine-5-)-Methyltransferase 1
  • DNA (Cytosine-5-)-Methyltransferases / genetics
  • DNA (Cytosine-5-)-Methyltransferases / metabolism*
  • DNA Methylation
  • Exons
  • Female
  • Gene Expression / genetics*
  • Gene Expression Regulation*
  • Humans
  • Male
  • Middle Aged
  • Postmortem Changes
  • Promoter Regions, Genetic
  • RNA, Messenger / metabolism
  • Receptor, Serotonin, 5-HT2A / genetics
  • Receptor, Serotonin, 5-HT2A / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction / methods
  • Statistics as Topic
  • Time Factors


  • RNA, Messenger
  • Receptor, Serotonin, 5-HT2A
  • DNA (Cytosine-5-)-Methyltransferase 1
  • DNA (Cytosine-5-)-Methyltransferases
  • DNMT1 protein, human