title: The Krüppel-like factor KLF15 inhibits transcription of the adrenomedullin gene in adipocytes.
abstract: 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.
authors.affiliation: Department of Internal Medicine, Division of Diabetes, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Tomoki
authors.initials: T
authors.lastname: Nagare
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sakaue
authors.forename: Mototsugu
authors.initials: M
authors.lastname: Takashima
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Takahashi
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Gomi
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Matsuki
authors.forename: Eijiro
authors.initials: E
authors.lastname: Watanabe
authors.forename: Ryuji
authors.initials: R
authors.lastname: Hiramatsu
authors.forename: Wataru
authors.initials: W
authors.lastname: Ogawa
authors.forename: Masato
authors.initials: M
authors.lastname: Kasuga
mesh_terms: D016475:3T3 Cells; D017667:Adipocytes / Q000378:metabolism*; D053607:Adrenomedullin / Q000037:antagonists & inhibitors / Q000235:genetics*; D000818:Animals; D047369:Chromatin Immunoprecipitation; D004268:DNA-Binding Proteins / Q000378:metabolism*; D015536:Down-Regulation; D005786:Gene Expression Regulation; D006801:Humans; D051741:Kruppel-Like Transcription Factors; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D011401:Promoter Regions, Genetic; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D004268:DNA-Binding Proteins; C467418:Klf15 protein, mouse; D051741:Kruppel-Like Transcription Factors; D014157:Transcription Factors; D053607:Adrenomedullin