کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8288753 | 1536264 | 2018 | 12 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Promoter analysis and transcriptional regulation of human carbonic anhydrase VIII gene in a MERRF disease cell model
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کلمات کلیدی
AP-2Specificity protein 1 (SP1)TSAPTMseGFPMERRFshRNAActivator protein-2HDACIP3R1Inositol trisphosphateIP3RTGMitochondrial DNA - DNA میتوکندریاDNA - DNA یا اسید دزوکسی ریبونوکلئیکshort hairpin RNA - RNA موی سر کوتاهSp1 - SP1deoxyribonucleic acid - اسید deoxyribonucleicTrichostatin A - تریکوستاتین Apost-translational modifications - تغییرات پس از ترجمه، پیرایش پساترجمهmtDNA - دیانای میتوکندریاییGene transcription - رونویسی ژنhuman embryonic kidney cells - سلول های کلیوی جنینی انسانHEK cells - سلولهای HEKmyoclonic epilepsy with ragged red fibers - صرع میوکلاونیک با اکسیژن قرمز پراکندهretrograde - عقب ماندگیSpecificity protein 1 - مشخصات پروتئین 1not significant - مهم نیستhistone deacetylase - هیستون داستیلازenhanced green fluorescent protein - پروتئین فلورسنت سبز افزایش یافته استPromoter - پروموترCarps - کپورها
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Myoclonic epilepsy with ragged-red fibers (MERRF) is a maternally inherited mitochondrial neuromuscular disease. We previously reported a significant decrease of mRNA and protein levels of nuclear DNA-encoded carbonic anhydrase VIII (CA8) in MERRF cybrids harboring A8344G mutation in mitochondrial DNA (mtDNA). In this study, we established a reporter construct of luciferase gene-carrying hCA8 promoter containing several putative transcription factor-binding sites, including GC-box, AP-2 and TATA-binding element in the 5'flanking region of the hCA8 gene. Using a series of mutated hCA8 promoter constructs, we demonstrated that a proximal GC-box, recognized by Sp1 and other Sp family members, may be a key cis-element functioning at the promoter. Additionally, a significant increase of the hCA8 promoter activity was observed in the wild-type and mutant cybrids with over-expression of eGFP-Sp1, but no detectable increase in the CA8 protein expression. In contrast, over-expression of Flag-Sp1 and Flag-Sp4 significantly increased the hCA8 promoter activity as well as endogenous CA8 protein expression in neuron-like HEK-293â¯T cells. However, down-regulation of Sp1, but not Sp4, in 293â¯T cells revealed a significant reduction of CA8 expression, suggesting that Sp1 is a predominant transcription factor for regulation of CA8 activity. Furthermore, our data indicate that chromatin structure may be involved in the expression of hCA8 gene in MERRF cybrids. Taken together, these results suggest that Sp1 transactivates hCA8 gene through the proximal GC box element in the promoter region. The key modulator-responsive factor to the mtDNA mutation and how it may affect nuclear hCA8 gene transcription need further investigations.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Archives of Biochemistry and Biophysics - Volume 641, 1 March 2018, Pages 50-61
Journal: Archives of Biochemistry and Biophysics - Volume 641, 1 March 2018, Pages 50-61
نویسندگان
Che-Min Lo, Yi-Shing Ma, Yau-Huei Wei, Benjamin Y.T. Hsieh, Mingli Hsieh,