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Pitx3 activates mouse tyrosine hydroxylase promoter via a high‐affinity binding site
Author(s) -
Lebel Mélanie,
Gauthier Yves,
Moreau Alain,
Drouin Jacques
Publication year - 2001
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 - 10.1046/j.1471-4159.2001.00257.x
Subject(s) - tyrosine hydroxylase , transcription factor , dopaminergic , homeobox , biology , promoter , dopamine , binding site , microbiology and biotechnology , gene , gene expression , neuroscience , genetics
Tyrosine hydroxylase (TH) is the rate‐limiting enzyme of dopamine and (nor)adrenaline biosynthesis. Regulation of its gene expression is complex and different regulatory mechanisms appear to be operative in various neuronal lineages. Pitx3, a homeodomain‐containing transcription factor, has been cloned from neuronal tissues and, in the CNS, mouse Pitx3 is exclusively expressed in midbrain dopaminergic (MesDA) neurons from embryonic day 11 (E11). TH appears in these neurons at E11.5, consistent with a putative role of Pitx3 in TH transcription. We show that Pitx3 activates the TH promoter through direct interaction with a single high‐affinity binding site within the promoter and that this site is sufficient for Pitx3 responsiveness. In contrast, we did not observe an effect of Nurr1, an orphan nuclear receptor essential for normal development of MesDA neurons, on TH promoter activity. Pitx3 activation of TH promoter activity appears to be cell‐dependent suggesting that Pitx3 action may be modulated by other(s) regulatory mechanism(s) and factor(s).