PMID: 9191094Jun 1, 1997Paper

Tissue-specific methylation occurs in the essential promoter element of the tyrosine hydroxylase gene

Brain Research. Molecular Brain Research
K OkuseK Kurihara

Abstract

Expression of tyrosine hydroxylase (TH) is regulated in a tissue-specific manner by multiple mechanisms. In catecholaminergic cells, the expression of TH-mRNA is up-regulated by forskolin (FK) and is suppressed by retinoic acid (RA). We have previously provided evidence that, in N-18 cells, the expression of TH-mRNA is suppressed by DNA methylation of the TH gene itself. In the present study, using a catecholaminergic cell line, N1E-115, we performed deletional and mutational analyses on the 5'-flanking region of the mouse TH gene. The results indicate that a cAMP response element (CRE) mediates constitutive transcription of the TH gene, as well as responsiveness to FK and RA. Using bisulfite sequencing methods, we analyzed the methylation status of the TH gene 5'-flanking region in various cell lines and rat tissues. We found that three cytosine residues in the domain surrounding the CRE of the TH gene promoter were specifically methylated in N-18 cells and TH non-expressing rat tissues. In contrast, these cytosines were undermethylated in TH expressing cell lines and tissues. The inverse correlation between the frequency of cytosine methylation at these specific sites and the levels of TH expression supports a role for DNA me...Continue Reading

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Citations

Dec 4, 2003·Biochemical and Biophysical Research Communications·Hee-Sun KimKwang-Soo Kim
Jan 3, 2001·Brain Research·J H BoatrightD E Borst
Aug 2, 2011·International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience·Robert Lenartowski, Anna Goc
Oct 18, 2011·Biochemical and Biophysical Research Communications·Jae Won YangMyung Ae Lee
Apr 13, 2004·American Journal of Physiology. Gastrointestinal and Liver Physiology·Kiran K NagothuAdhip P N Majumdar
Dec 14, 1999·The Journal of Biological Chemistry·P K SenguptaB D Smith
Nov 30, 2000·American Journal of Physiology. Gastrointestinal and Liver Physiology·Z DongB M Evers
Sep 6, 2001·Oncogene·D N DiNardoD I Rodenhiser

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