Analysis of the guinea-pig estrogen-regulated gec1/GABARAPL1 gene promoter and identification of a functional ERE in the first exon.
The gec1/GABARAPL1 (GABA(A)-receptor-associated protein like-1) gene has been identified as an early estrogen-regulated gene in guinea-pig cultured endometrial glandular epithelial cells (GEC). Guinea-pig and human gec1/GABARAPL1 proteins share 87% identity with GABARAP, which acts as a protein linker between microtubules and the GABA(A) receptor. To investigate the molecular mechanisms regulating gec1/GABARAPL1 gene expression, the 1.5-kbp region upstream of the translation initiation codon of the guinea-pig gec1/GABARAPL1 gene was cloned. A 300-bp fragment encompassing a pyrimidine-rich initiator element (INR) and the transcription start site (+1) was sufficient to initiate transcription. Transfection and gel shift experiments showed that a sequence located at +36/+50 in the first exon permitted induction of expression of this gene by estradiol acting via ERalpha. This sequence (GGGTCAACGTGACGT) differs only by one base pair from the consensus estrogen response element ERE (GGGTCAACGTGACCT). It can be concluded that the ERE located in the first exon encoding the 5'-untranslated region is sufficient for E2 activation of gec1/GABARAPL1 transcription.
Vernier-Magnin
Sandrine
S
Laboratoire de Biochimie Biologie Moléculaire, EA3922 Estrogènes, Expression Génique et Pathologies du Système Nerveux Central, IFR 133, Université de Franche-Comté, U.F.R. Sciences et Techniques, 16 route de Gray, 25030 Besançon cedex, France.
Nemos
Christophe
C
Mansuy
Virginie
V
Tolle
Fabrice
F
Guichard
Laure
L
Delage-Mourroux
Régis
R
Jouvenot
Michèle
M
Fraichard
Annick
A
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001483:Base Sequence; D016466:CHO Cells; D006224:Cricetinae; D004958:Estradiol / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000096:biosynthesis / Q000378:metabolism; D004967:Estrogens / Q000494:pharmacology*; D005091:Exons; D005260:Female; D005786:Gene Expression Regulation; D006168:Guinea Pigs; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis / Q000235:genetics*; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000235:genetics*; D020218:Response Elements / Q000235:genetics*; D024363:Transcription Initiation Site
D048868:Adaptor Proteins, Signal Transducing; D047628:Estrogen Receptor alpha; D004967:Estrogens; C430503:GABARAPL1 protein, human; D008869:Microtubule-Associated Proteins; D004958:Estradiol