Nagare Tomoki, Sakaue Hiroshi, Takashima Mototsugu, Takahashi Kazuhiro, Gomi Hideyuki, Matsuki Yasushi, Watanabe Eijiro, Hiramatsu Ryuji, Ogawa Wataru, Kasuga Masato
Department of Internal Medicine, Division of Diabetes, Kobe University Graduate School of Medicine, Kobe, Japan.
Biochem Biophys Res Commun. 2009 Jan 30;379(1):98-103. doi: 10.1016/j.bbrc.2008.12.020. Epub 2008 Dec 16.
KLF15 (Krüppel-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.
KLF15（Krüppel样因子15）通过激活其靶基因，在脂肪细胞分化和脂肪细胞中的葡萄糖转运中发挥关键作用。我们现在利用基于微阵列的染色质免疫沉淀和基因表达分析相结合的方法，在3T3-L1小鼠脂肪细胞中鉴定出了六个由KLF15直接调控的靶基因。我们在3T3-L1前脂肪细胞和脂肪细胞中使用荧光素酶报告基因测定法，证实了KLF15对这些基因之一（肾上腺髓质素基因）的直接调控。此类分析表明，人肾上腺髓质素基因启动子中最靠近上游的CACCC元件（位于跨越核苷酸-70和-29的区域）是KLF15进行反式抑制所必需的。此外，染色质免疫沉淀显示，KLF15在培养的人脂肪细胞中与该人肾上腺髓质素基因启动子区域结合。因此，这些结果表明KLF15参与脂肪组织中肾上腺髓质素表达的调控。
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