Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1998-10-22
pubmed:abstractText
Tyrosine hydroxylase (TH), the rate-limiting enzyme in the biosynthesis of catecholamine neurotransmitters, is expressed in a restricted number of areas, and subject to numerous regulations during development and in adulthood. Two transcription factor binding sites present in the proximal region of the TH gene, the TPA-responsive element (TRE) and the c-AMP responsive element (CRE), have been shown to play important roles in TH gene regulation in vitro. In order to elucidate in vivo the role of these two sites, we produced transgenic mice bearing a 5.3-kb fragment from the 5' flanking sequence of the TH gene with mutations in either the CRE-or TRE-sites. Using the intact 5.3-kb fragment fused to two different reporter genes (HSV1-tk and lacZ), we show that this promoter fragment is able to specifically direct expression in catecholaminergic tissues both in adult mice and embryos. Interestingly, the CRE- and TRE-mutated transgenes were not expressed in adult mice, contrary to the situation in embryos where they were specifically expressed in catecholaminergic regions. These results demonstrate that the CRE and TRE play an essential role in basal TH expression in adult tissues in vivo. Moreover, they suggest that distinct transcription factors are involved in TH regulation in developing and adult tissues. In support of this, gel mobility shift experiments revealed a complex present only in embryonic tissues. Taken together, these data highlight the diversity of the mechanisms underlying the establishment and maintenance of the catecholaminergic phenotype.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0953-816X
pubmed:author
pubmed:issnType
Print
pubmed:volume
10
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
508-21
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:9749713-Adrenal Medulla, pubmed-meshheading:9749713-Aging, pubmed-meshheading:9749713-Animals, pubmed-meshheading:9749713-Brain, pubmed-meshheading:9749713-Brain Chemistry, pubmed-meshheading:9749713-Coloring Agents, pubmed-meshheading:9749713-Cyclic AMP Response Element Modulator, pubmed-meshheading:9749713-DNA-Binding Proteins, pubmed-meshheading:9749713-Female, pubmed-meshheading:9749713-Gene Expression Regulation, Developmental, pubmed-meshheading:9749713-Gene Expression Regulation, Enzymologic, pubmed-meshheading:9749713-Immunohistochemistry, pubmed-meshheading:9749713-Mice, pubmed-meshheading:9749713-Mutation, pubmed-meshheading:9749713-Plasmids, pubmed-meshheading:9749713-Pregnancy, pubmed-meshheading:9749713-Repressor Proteins, pubmed-meshheading:9749713-Tyrosine 3-Monooxygenase
pubmed:year
1998
pubmed:articleTitle
CRE and TRE sequences of the rat tyrosine hydroxylase promoter are required for TH basal expression in adult mice but not in the embryo.
pubmed:affiliation
Laboratoire de Génétique Moléculaire de la Neurotransmission et des Processus Neurodégératifs, CNRS-UMR C9923, Hôpital de la Pitié Salpêtrière, Paris, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't