The tissue-specific methylation of the human Tyrosine Hydroxylase gene reveals new regulatory elements in the first exon

Tamás Arányi, Baptiste A. Faucheux, Olfa Khalfallah, Guilan Vodjdani, Nicole Faucon Biguet, Jacques Mallet, Rolando Meloni

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The methylation status of CpG dinucleotides located in or near regulatory elements affects gene expression. The CpG-rich sequence located outside the 5́ promoter region of the human Tyrosine Hydroxylase (TH) gene appears to influence the functional effect of the adjacent intronic HUMTH01 microsatellite. In order to identify new regulatory elements in this region acting on gene expression, the methylation profile of the TH CpG island was investigated using the bisulfite sequencing method. The overall methylation level of this region is correlated to TH-expressing and non-expressing status in cell lines and DNA demethylation treatment with 5-azacytidine increased TH expression. Moreover, in a homogeneous background of methylated CpGs, a single CpG in the first exon of the gene is constantly either unmethylated or methylated in, respectively, TH-expressing or non-expressing cell lines, tissues and single cells. Further analysis ascertained that this CpG is contained in a sequence characterized by putative binding sites for the AP2, Sp1 and KAISO factors. Characterization of this sequence shows that these factors specifically bind their respective sites. Finally, the binding of KAISO, a transcriptional repressor, is conditioned by the methylation of this sequence, which may, thus, participate in the regulation of TH gene expression according to its methylation pattern.

Original languageEnglish
Pages (from-to)129-139
Number of pages11
JournalJournal of neurochemistry
Issue number1
Publication statusPublished - Jul 13 2005



  • Bisulfite sequencing
  • CpG island
  • DNA methylation
  • Gene expression
  • Tyrosine hydroxylase

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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