A tetranucleotide polymorphic microsatellite, located in the first intron of the tyrosine hydroxylase gene, acts as a transcription regulatory element in vitro

被引:134
作者
Meloni, R [1 ]
Albanese, V [1 ]
Ravassard, P [1 ]
Treilhou, F [1 ]
Mallet, J [1 ]
机构
[1] Hop La Pitie Salpetriere, CNRS, UMR9923, Lab Genet Neurotrasmiss & Processus Neurodegenera, F-75013 Paris, France
关键词
D O I
10.1093/hmg/7.3.423
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The polymorphic HUMTH01 microsatellite, located in the first intron of the tyrosine hydroxylase gene is characterized by a tetranucleotide core motif, The 10 repeat allele of this microsatellite exhibits two sequence variants: an imperfect repeat and a perfect repeat, Here we present evidence that this tetrarepeat is endowed with regulatory properties, Constructions were made linking the 10 repetition alleles to the luciferase reporter gene under the control of a thymidine kinase minimal promoter, In transient transfection experiments in HeLa, PC12 and SK-NSH cell lines these repeated sequences increased the basal transcription up to 9-fold. This effect was independent of the sequence orientation, a feature characteristic of an enhancer element, In electrophoretic mobility shift assays these tetrameric repeated sequences form specific complexes with HeLa cell nuclear extracts, Competition experiments with heterologous sequences suggest that proteins of the Fos-Jun family may be involved in the formation of these complexes, although other unidentified transacting factors bind to these sequences, These results thus implicate the HUMTH01 microsatellite in the regulation of tyrosine hydroxylase gene expression, Tetrarepeated sequences of this type may constitute a new class of regulatory elements.
引用
收藏
页码:423 / 428
页数:6
相关论文
共 44 条
[21]   The TiPS/TINS lecture. Catecholamines: From gene regulation to neuropsychiatric disorders [J].
Mallet, J .
TRENDS IN PHARMACOLOGICAL SCIENCES, 1996, 17 (04) :129-135
[22]   ASSOCIATION OF MANIC-DEPRESSIVE ILLNESS WITH TYROSINE-HYDROXYLASE MICROSATELLITE MARKER [J].
MELONI, R ;
LEBOYER, M ;
BELLIVIER, F ;
BARBE, B ;
SAMOLYK, D ;
ALLILAIRE, JF ;
MALLET, J .
LANCET, 1995, 345 (8954) :932-932
[23]  
MELONI R, 1995, CR ACAD SCI III-VIE, V318, P803
[24]  
MEYER E, 1995, J MOL EVOL, V41, P10
[25]  
MOORE S, 1991, GENOMICS, V10, P564
[26]   LINKAGE OF TYROSINE-HYDROXYLASE TO 4 OTHER MARKERS ON THE SHORT ARM OF CHROMOSOME 11 [J].
MOSS, PAH ;
DAVIES, KE ;
BONI, C ;
MALLET, J ;
REEDERS, ST .
NUCLEIC ACIDS RESEARCH, 1986, 14 (24) :9927-9932
[27]   A WEAK ASSOCIATION BETWEEN TH AND DRD2 GENES AND BIPOLAR AFFECTIVE-DISORDER IN A SPANISH SAMPLE [J].
PEREZ DE CASTRO, I ;
SANTOS, J ;
TORRES, P ;
VISEDO, G ;
SAIZRUIZ, J ;
LLINARES, C ;
FERNANDEZPIQUERAS, J .
JOURNAL OF MEDICAL GENETICS, 1995, 32 (02) :131-134
[28]  
POLYMEROPOULOS MH, 1991, NUCLEIC ACIDS RES, V19, P3753, DOI 10.1093/nar/19.13.3753
[29]  
PUERS C, 1993, AM J HUM GENET, V53, P953
[30]   FRAGILE-X SYNDROME UNSTABLE ELEMENT, P(CCG)N, AND OTHER SIMPLE TANDEM REPEAT SEQUENCES ARE BINDING-SITES FOR SPECIFIC NUCLEAR PROTEINS [J].
RICHARDS, RI ;
HOLMAN, K ;
YU, S ;
SUTHERLAND, GR .
HUMAN MOLECULAR GENETICS, 1993, 2 (09) :1429-1435