[Cytosine demethylation in the tyrosine hydroxylase gene promoter in the hypothalamus cells of the rat brain under the action of an aminoadamantane derivative Ladasten].
In our previous study of mechanisms of pharmacological activity of a derivative of 2-aminoadamantane, Ladasten, we have shown more than a twofold increase in the mRNA level of the tyrosine hydroxylase (TH) gene in the rat brain hypothalamus 1.5-2 h after a single administration of this substance. In the present study, we employed the bisulfate sequencing technique to detect changes of GpG islands methylation status in the TH gene 5'-flanking region (-650 + 84) in hypothalamus cells of control and experimental rats after a single exposure to Ladasten. Ladasten was shown to increase frequency of cytosine demethylation in binding sites of some transcription factors or in neighboring motifs. It is suggested that the Ladasten-induced increase of TH gene transcriptional activity in rat hypothalamus is associated with cytosine demethylation in CpG islands in some regulatory gene elements.
Vakhitova
Iu V
IuV
Sadovnikov
S V
SV
Iamidanov
R S
RS
Seredenin
S B
SB
D000218:Adamantane / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D018899:CpG Islands; D003596:Cytosine / Q000378:metabolism*; D019175:DNA Methylation / Q000187:drug effects*; D007031:Hypothalamus / Q000378:metabolism*; D008297:Male; D011401:Promoter Regions, Genetic; D051381:Rats; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics / Q000378:metabolism*
C493151:N-(2-adamantyl)-N-p-bromophenylamine; D014157:Transcription Factors; D003596:Cytosine; D014446:Tyrosine 3-Monooxygenase; D000218:Adamantane