کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10749715 | 1050294 | 2016 | 7 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Transcriptional regulation of the human Liver X Receptor α gene by Hepatocyte Nuclear Factor 4α
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کلمات کلیدی
HDLHNF-4αHNF-4LXRRCTHRELXRsDNAPPPARABCA1SREBP-1cChIP-SeqshRNAshort interfering RNA - RNA تداخل کوتاهshort hairpin RNA - RNA موی سر کوتاهsiRNA - siRNAOxysterols - اکسستیرولchromatin immunoprecipitation - ایمن سازی کروماتینGene regulation - تنظیم ژنHepatocyte nuclear factor 4 - عامل هسته ای هپاتوسیت 4Hormone response element - عنصر پاسخ هورمونSterol regulatory element binding protein 1c - پروتئین اتصال دهنده پروتئین Sterol 1cCHiP - چیپreverse cholesterol transport - کلسترول معکوس حمل و نقلperoxisome proliferator-activated receptor - گیرنده فعال فعال پروکسیومLiver X receptors - گیرنده های کبد XNuclear receptor - گیرنده هستهای، گیرندههای هستهای
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Transcriptional regulation of the human Liver X Receptor α gene by Hepatocyte Nuclear Factor 4α Transcriptional regulation of the human Liver X Receptor α gene by Hepatocyte Nuclear Factor 4α](/preview/png/10749715.png)
چکیده انگلیسی
Liver X Receptors (LXRs) are sterol-activated transcription factors that play major roles in cellular cholesterol homeostasis, HDL biogenesis and reverse cholesterol transport. The aim of the present study was to investigate the mechanisms that control the expression of the human LXRα gene in hepatic cells. A series of reporter plasmids containing consecutive 5â² deletions of the hLXRα promoter upstream of the luciferase gene were constructed and the activity of each construct was measured in HepG2 cells. This analysis showed that the activity of the human LXRα promoter was significantly reduced by deleting the â111 to â42 region suggesting the presence of positive regulatory elements in this short proximal fragment. Bioinformatics data including motif search and ChIP-Seq revealed the presence of a potential binding motif for Hepatocyte Nuclear Factor 4 α (HNF-4α) in this area. Overexpression of HNF-4α in HEK 293T cells increased the expression of all LXRα promoter constructs except â42/+384. In line, silencing the expression of endogenous HNF-4α in HepG2 cells was associated with reduced LXRα protein levels and reduced activity of the â111/+384 LXRα promoter but not of the â42/+384 promoter. Using ChiP assays in HepG2 cells combined with DNAP assays we mapped the novel HNF-4α specific binding motif (H4-SBM) in the â50 to â40 region of the human LXRα promoter. A triple mutation in this H4-SBM abolished HNF-4α binding and reduced the activity of the promoter to 65% relative to the wild type. Furthermore, the mutant promoter could not be transactivated by HNF-4α. In conclusion, our data indicate that HNF-4α may have a wider role in cell and plasma cholesterol homeostasis by controlling the expression of LXRα in hepatic cells.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical and Biophysical Research Communications - Volume 469, Issue 3, 15 January 2016, Pages 573-579
Journal: Biochemical and Biophysical Research Communications - Volume 469, Issue 3, 15 January 2016, Pages 573-579
نویسندگان
Dimitris Theofilatos, Aristomenis Anestis, Koshi Hashimoto, Dimitris Kardassis,