Analysis of the guinea-pig estrogen-regulated gec1/GABARAPL1 gene promoter and identification of a functional ERE in the first exon

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• 作者：Sandrine Vernier-Magnin ; Christophe Nemos ; Virginie Mansuy ; Fabrice Tolle ; Laure Guichard ; Ré ; gis Delage-Mourroux ; Michè ; le Jouvenot and Annick Fraichard
• 关键词：17β ; -estradiol (E₂) ; Early estrogen-regulated gene ; ERE (estrogen response element) ; INR (initiator element) ; Estrogen receptors (ERα ; and ERβ ; ) ; gec1/GABARAPL1
• 刊名：Biochimica et Biophysica Acta (BBA)/Gene Structure and Expression
• 出版年：2005
• 出版时间：2005
• 年：2005
• 卷：1731
• 期：1
• 页码：23-31
• 全文大小：486 K

文摘

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 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.