TY - JOUR
T1 - Analysis of the guinea-pig estrogen-regulated gec1/GABARAPL1 gene promoter and identification of a functional ERE in the first exon
AU - Vernier-Magnin, Sandrine
AU - Nemos, Christophe
AU - Mansuy, Virginie
AU - Tolle, Fabrice
AU - Guichard, Laure
AU - Delage-Mourroux, Régis
AU - Jouvenot, Michèle
AU - Fraichard, Annick
N1 - Funding Information:
This research work was supported by a fellowship from Ministère de l'Enseignement Supérieur et de la Recherche (MESR) and by grants from MESR (EA 3922) and Ligue Nationale Contre le Cancer (Comité du Doubs and Comité du Jura). We thank C. Garenc for statistical analysis. We are grateful to AstraZeneca (Reims, France) for providing antiestrogen ICI 182 780, to E. Enmark and P. Chambon for generous gift of ERα and ERβ expression plasmids and to B. Katzenellenbogen for generous gift of the reporter plasmid 2ERE-pS2-Luc.
PY - 2005/10/15
Y1 - 2005/10/15
N2 - The gec1/GABARAPL1 (GABAA-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 GABAA 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 ERα. 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.
AB - The gec1/GABARAPL1 (GABAA-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 GABAA 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 ERα. 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.
KW - 17β-estradiol (E)
KW - ERE (estrogen response element)
KW - Early estrogen-regulated gene
KW - Estrogen receptors (ERα and ERβ)
KW - INR (initiator element)
KW - gec1/GABARAPL1
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U2 - 10.1016/j.bbaexp.2005.05.002
DO - 10.1016/j.bbaexp.2005.05.002
M3 - Article
C2 - 16153720
AN - SCOPUS:26844432248
SN - 0167-4781
VL - 1731
SP - 23
EP - 31
JO - Biochimica et Biophysica Acta - Gene Structure and Expression
JF - Biochimica et Biophysica Acta - Gene Structure and Expression
IS - 1
ER -