Identification of nuclear factor-¦ÊB sites in the Slc2a4 gene promoter

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• 作者：D.T. Furuya^a ; ^{danifuruya@yahoo.com} ; E.A. Neri^a ; A.C. Poletto^a ; G.F. Anh&ecirc ; ^b ; H.S. Freitas^a ; R.S. Campello^a ; N.A. Rebou&ccedil ; as^a ; U.F. Machado^a ;
• 关键词：ChIP ; chromatin immunoprecipitation ; EMSA ; eletrophoretic mobility shift assay ; GLUT ; glucose transporter ; I¦ÊB ; inhibitor of nuclear factor-¦ÊB ; IKK ; I¦ÊB kinase ; NF ; nuclear factor ; Slc ; solute carrier ; TNF ; tumor nuclear factor ; WAT ; white adipose tiss
• 刊名：Molecular and Cellular Endocrinology
• 出版年：2013
• 出版时间：6 May, 2013
• 年：2013
• 卷：370
• 期：1-2
• 页码：87-95
• 全文大小：1115 K

文摘

Glucose transporter GLUT4 protein, codified by Slc2a4 gene plays a key role in glycemic homeostasis. Insulin resistance, as in obesity, has been associated to inflammatory state, in which decreased GLUT4 is a feature. Inflammatory NF-¦ÊB transcriptional factor has been proposed as a repressor of Slc2a4; although, the binding site(s) in Slc2a4 promoter and the direct repressor effect have never been reported yet. A motif-based sequence analysis of mouse Slc2a4 promoter revealed two putative ¦ÊB sites located inside ?83/?62 and ?134/?113 bp. Eletrophoretic mobility assay showed that p50 and p65 NF-¦ÊB subunits bind to both putative ¦ÊB sites. Chromatin immunoprecipitation assay using genomic DNA from adipocytes confirmed p50- and p65-binding to Slc2a4 promoter. Moreover, transfection experiments revealed that NF-¦ÊB binds to the ?134/?113 bp region of the mouse Slc2a4 gene promoter, inhibiting the Slc2a4 gene transcription. The current findings demonstrate the existence of two ¦ÊB sites in Slc2a4 gene promote, and that NF-¦ÊB has a direct repressor effect upon the Slc2a4 gene, providing an important link between insulin resistance and inflammation.