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The tissue‐specific methylation of the human Tyrosine Hydroxylase gene reveals new regulatory elements in the first exon
Author(s) -
Arányi Tamás,
Faucheux Baptiste A.,
Khalfallah Olfa,
Vodjdani Guilan,
Biguet Nicole Faucon,
Mallet Jacques,
Meloni Rolando
Publication year - 2005
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2005.03173.x
Subject(s) - cpg site , dna methylation , methylation , biology , epigenetics of physical exercise , exon , bisulfite sequencing , gene , microbiology and biotechnology , regulation of gene expression , regulatory sequence , epigenetics , genetics , gene expression , differentially methylated regions , promoter
The methylation status of CpG dinucleotides located in or near regulatory elements affects gene expression. The CpG‐rich sequence located outside the 5′ 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.