The Kruppel-like factor KLF15 inhibits transcription of the adrenomedullin gene in adipocytes
The Kruppel-like factor KLF15 inhibits transcription of the adrenomedullin gene in adipocytes
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DOI：
10.1016/j.bbrc.2008.12.020
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发表时间：
2009-01-30
影响因子：
3.1
通讯作者：
Kasuga, Masato
中科院分区：
文献类型：
--
作者：
Nagare, Tomoki;Sakaue, Hiroshi;Kasuga, Masato
KLF15(Kruppel-like factor15)通过激活其靶基因，在脂肪细胞分化和葡萄糖转运中发挥关键作用。我们现在结合基于微阵列的染色质免疫沉淀和基因表达分析，在3T3-L1小鼠脂肪细胞中鉴定了KLF15直接调控的六个靶基因。我们通过在3T3-L1前脂肪细胞和脂肪细胞中使用荧光素酶报告实验证实了KLF15对其中一个基因的直接调节，即对肾上腺髓质素的调节。分析表明，人肾上腺髓质素基因启动子最近端的CACCC元件(位于核苷酸-70和-29区域)是KLF15反式抑制所必需的。此外，染色质免疫沉淀显示KLF15与培养的人脂肪细胞中人肾上腺髓质素基因启动子的这一区域结合。这些结果表明KLF15参与调节脂肪组织中肾上腺髓质素的表达。(C)2008 Elsevier Inc.保留所有权利。
KLF15 (Kruppel-like Factor 15) plays a key role in adipocyte differentiation and glucose transport in adipocytes through activation of its target genes. We have now identified six target genes regulated directly by KLF15 in 3T3-L1 mouse adipocytes with the use of a combination of microarray-based chromatin immunoprecipitation and gene expression analyses. We confirmed the direct regulation by KLF15 of one of these genes, that for adrenomedullin, with the use of a luciferase reporter assay in 3T3-L1 preadipocytes and adipocytes. Such analysis revealed that the most proximal CACCC element in the promoter of the human adrenomedullin gene (located in the region spanning nucleotides -70 and -29) is required for trans-inhibition by KLF15. Furthermore, chromatin immunoprecipitation showed that KLF15 binds to this region of the human adrenomedullin gene promoter in Cultured human adipocytes. These results thus implicate KLF15 in the regulation of adrenomedullin expression in adipose tissue. (C) 2008 Elsevier Inc. All rights reserved.