کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5907617 | 1569875 | 2010 | 7 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Identification of a FOXA-dependent enhancer of human alcohol dehydrogenase 4 (ADH4)
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کلمات کلیدی
ADHSV40 promoterElectrophoretic mobility shift assay - آزمون تحرک تحرک الکتروفورزAlcohol dehydrogenase - الکل دهیدروژنازAlcoholism - الکلیسمGene regulation - تنظیم ژنEMSA یا electrophoretic mobility shift assay - سنجش تغییر تحرک الکتروفورتیکTranscription factor - عامل رونویسیHaplotype - هاپلوتیپpolymerase chain reaction - واکنش زنجیره ای پلیمرازPCR - واکنش زنجیرهٔ پلیمرازPolymorphisms - پلی مورفیسمSingle nucleotide polymorphism - پلیمورفیسم تک نوکلئوتیدیSNP - چندریختی تک-نوکلئوتید
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
ژنتیک
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Identification of a FOXA-dependent enhancer of human alcohol dehydrogenase 4 (ADH4) Identification of a FOXA-dependent enhancer of human alcohol dehydrogenase 4 (ADH4)](/preview/png/5907617.png)
چکیده انگلیسی
Human alcohol dehydrogenase 4 (ADH4) is one of the key enzymes involved in the metabolism of alcohol. ADH4 is highly expressed in the liver, and previous studies have revealed several cis-acting elements in the proximal promoter region. In this study we have identified a distal upstream enhancer, 4E, of ADH4. In HepG2 human hepatoma cells, 4E increased the activity of an ADH4 basal promoter by 50-fold. 4E was cell-specific, as no enhancer activity was detected in a human lung cell line, H1299. We have narrowed the enhancer activity to a 565Â bp region and have identified multiple liver-enriched transcription factor binding sites in the region. By electrophoretic mobility shift assays, we confirmed binding of FOXA proteins to these sites. Site-directed mutagenesis studies demonstrated that sites 1 and 4 have the biggest effect on enhancer function, and mutations in multiple sites have multiplicative effects. We also studied the effects of three variations in the minimal enhancer region. Two variations had a significant effect on enhancer activity, decreasing the activity to 0.6-fold, while one had small but significant effect. The differences in the functional activity in different haplotypes suggest that this region could play an important role in the risk for alcoholism.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Gene - Volume 460, Issues 1â2, 15 July 2010, Pages 1-7
Journal: Gene - Volume 460, Issues 1â2, 15 July 2010, Pages 1-7
نویسندگان
Sirisha Pochareddy, Howard J. Edenberg,