The human tyrosine hydroxylase gene promoter

13.329 kilobases of the single copy human tyrosine hydroxylase (hTH) gene were isolated from a genomic library. The 5′ flanking 11 kilobases fused to the reporter green fluorescent protein (GFP) drove high level expression in TH+ cells of the substantia nigra of embryonic and adult transgenic mice a...

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Vydané v:	Brain research. Molecular brain research. Ročník 112; číslo 1; s. 8 - 23
Hlavní autori:	Kessler, Mark A., Yang, Ming, Gollomp, Kandace L., Jin, Hao, Iacovitti, Lorraine
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	Amsterdam Elsevier B.V 10.04.2003 Elsevier
Predmet:	Alcoholism Animals Basal Ganglia - cytology Basal Ganglia - enzymology Bicoid Biological and medical sciences Brain Brain Diseases - enzymology Brain Diseases - genetics Catecholamines Cell Differentiation - genetics CNS Development Dopamine Dopamine - biosynthesis Dopaminergic neurons EGFP Female Fetus Fundamental and applied biological sciences. Psychology Gene Expression Regulation, Enzymologic - genetics Genes. Genome Genetics GFP Goosecoid-like Green Fluorescent Proteins Gscl HNF-3beta HOXA4 HOXA5 Human Humans Luminescent Proteins Mice Mice, Transgenic Molecular and cellular biology Molecular genetics Molecular Sequence Data Movement disorders Mutation - genetics Neuron restrictive silencer element Neurons Neurons - enzymology NR4A2 NRSE Nurr1 Parkinson’s disease Pitx3 Promoter Promoter Regions, Genetic - genetics Rats Sequence Homology, Nucleic Acid Stem cells Substantia Nigra - cytology Substantia Nigra - embryology Substantia Nigra - enzymology Transgene Transgenic mice Transplantation Tyrosine 3-Monooxygenase - biosynthesis Tyrosine 3-Monooxygenase - genetics Tyrosine hydroxylase Brain HNF-3beta CNS Tyrosine hydroxylase Transplantation EGFP GFP Promoter Dopaminergic neurons Gscl Development Neuron restrictive silencer element Genetics HOXA5 Movement disorders HOXA4 Human Dopamine Neurons Alcoholism Transgenic mice Nurr1 Cellular and molecular biology Catecholamines Goosecoid-like Transgene Pitx3 NR4A2 NRSE Stem cells Bicoid Parkinson’s disease Transcription promoter Tyrosine 3-monooxygenase Gene CNS: Parkinson's disease Enzyme Nurrl Oxidoreductases
ISSN:	0169-328X, 1872-6941
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Shrnutí:	13.329 kilobases of the single copy human tyrosine hydroxylase (hTH) gene were isolated from a genomic library. The 5′ flanking 11 kilobases fused to the reporter green fluorescent protein (GFP) drove high level expression in TH+ cells of the substantia nigra of embryonic and adult transgenic mice as determined by double label fluorescence microscopy. To provide a basis for future analysis of polymorphisms and structure–function studies, the previously unreported distal 10.5 kilobases of the hTH promoter were sequenced with an average coverage of 20-fold, the remainder with 4-fold coverage. Sequence features identified included four perfect matches to the bicoid binding element (BBE, consensus: BBTAATCYV) all of which exhibited specific binding by electrophoretic mobility shift assay (EMSA). Comparison to published sequences of mouse and rat TH promoters revealed five areas of exceptional homology shared by these species in the upstream TH promoter region −2 kb to −9 kb relative to the transcription start site. Within these conserved regions (CRs I–V), potential recognition sites for NR4A2 (Nurr1), HNF-3beta, HOXA4, and HOXA5 were shared across human, mouse, and rat TH promoters.
Bibliografia:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23
ISSN:	0169-328X 1872-6941
DOI:	10.1016/S0169-328X(02)00694-0