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Clonage par simple-hybride de facteurs de transcription régulant le gène de la tyrosine hydroxylase (TH) de rat

Abstract : Tyrosine hydroxylase is the rate limiting enzyme in catecholamine biosynthesis, a major group of neurotransmitters including dopamine, norepinephrine and epinephrine.

The aim of our work was to isolate transcription factors potentially implicated in the cell-specific expression of the rat TH gene. For this purpose, we used the yeast one-hybrid system to identify proteins interacting with 2 important elements present in the TH promoter : the E box and the octameric/heptameric sequences. Three cDNA clones were obtained from 2 different cDNA libraries (whole adult rat brain and embryonic rat mesencephalon). The first cDNA corresponds to rITF2, a bHLH factor which ability to bind to the TH E box has previously been described. The second one is Lhx9, a LIM homeobox protein. Finally, the third cDNA, which we named ZENON, encodes a novel zinc finger protein showing a neuronal specific expression. These 3 factors were further characterized, revealing quite interesting features. They bind specifically to the TH promoter and are able to modulate TH gene transcription in cell lines. All 3 clones exhibit complex and changing expression patterns throughout development, however this expression is not restricted to catecholaminergic cells. To better understand the function of these factors in TH cell-specific expression, the E box and the octameric/heptameric sequences were characterized in vivo in transgenic mice. The E box plays a subtle role in peripheral catecholaminergic cells, suggesting intricate mechanisms involved in TH cell-specific expression.

This work brings to light the difficulties underlying the search for transcription factors implicated in cell-specific expression mechanisms. Furthermore, our data defines a new zinc finger protein family, of which ZENON is the first member.
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https://tel.archives-ouvertes.fr/tel-00372111
Contributor : Hélène Kiefer Connect in order to contact the contributor
Submitted on : Tuesday, March 31, 2009 - 12:18:15 PM
Last modification on : Tuesday, August 2, 2022 - 4:31:26 AM
Long-term archiving on: : Thursday, June 10, 2010 - 7:21:14 PM

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Hélène Kiefer. Clonage par simple-hybride de facteurs de transcription régulant le gène de la tyrosine hydroxylase (TH) de rat. Sciences du Vivant [q-bio]. Institut national agronomique paris-grignon - INA P-G, 2002. Français. ⟨tel-00372111⟩

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