RNA interference-mediated inhibition of hepatocyte nuclear factor 1α identifies target genes

被引:4
作者
Evans, Joanne R. [2 ]
Kelly, David L. [3 ]
Morris, Kirsten J. [1 ]
Arvide, Elsa M. [1 ]
Harris, Ann [1 ,2 ]
机构
[1] Northwestern Univ, Feinberg Sch Med, Childrens Mem Res Ctr, Chicago, IL 60614 USA
[2] Univ Oxford, Weatherall Inst Mol Med, John Radcliffe Hosp, Oxford OX3 9DS, England
[3] Univ Nebraska, Med Ctr, Eppley Inst Res Canc & Allied Dis, Omaha, NE 68198 USA
来源
BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS | 2008年 / 1779卷 / 05期
关键词
hepatocyte nuclear factor alpha; RNA interference; transcriptional network;
D O I
10.1016/j.bbagrm.2008.03.002
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Hepatocyte nuclear factor 1 alpha (HNF1 alpha) is a homeodomain transcription factor that is central to co-ordinated differentiation of a number of cell lineages, including hepatocytes in the liver and islet cells in the pancreas. HNF1 alpha interacts directly with other transcription factors and co-factors and is involved in chromatin modification to alter gene expression. To further investigate the pivotal role of HNF1 alpha in transcriptional control pathways we utilized RNA interference. An siRNA oligonucleotide specific for HNF1 alpha reduced HNF1 alpha protein levels by up to 70% in transient transfections of Caco2 cells. The same sequence incorporated into an shRNAi reduced protein levels by up to 90% in stable transfections. Microarray analysis of RNA from cell lines with stable RNAi-mediated down-Fegulation of HNF1 alpha, identified genes known to be regulated by this transcription factor and also novel genes. (C) 2008 Elsevier B.V. All rights reserved.
引用
收藏
页码:341 / 346
页数:6
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