Dataset Information

Kruppel-like factor KLF8 plays a critical role in adipocyte differentiation.

ABSTRACT: KLF8 (Krüppel-like factor 8) is a zinc-finger transcription factor known to play an essential role in the regulation of the cell cycle, apoptosis, and differentiation. However, its physiological roles and functions in adipogenesis remain unclear. In the present study, we show that KLF8 acts as a key regulator controlling adipocyte differentiation. In 3T3-L1 preadipocytes, we found that KLF8 expression was induced during differentiation, which was followed by expression of peroxisome proliferator-activated receptor ? (PPAR?) and CCAAT/enhancer-binding protein ? (C/EBP?). Adipocyte differentiation was significantly attenuated by the addition of siRNA against KLF8, whereas overexpression of KLF8 resulted in enhanced differentiation. Furthermore, luciferase reporter assays demonstrated that overexpression of KLF8 induced PPAR?2 and C/EBP? promoter activity, suggesting that KLF8 is an upstream regulator of PPAR? and C/EBP?. The KLF8 binding sites were localized by site mutation analysis to -191 region in C/EBP? promoter and -303 region in PPAR? promoter, respectively. Taken together, these data reveal that KLF8 is a key component of the transcription factor network that controls terminal differentiation during adipogenesis.

SUBMITTER: Lee H

PROVIDER: S-EPMC3528641 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Krüppel-like factor KLF8 plays a critical role in adipocyte differentiation.

Lee Haemi H Kim Hyo Jung HJ Lee Yoo Jeong YJ Lee Min-Young MY Choi Hyeonjin H Lee Hyemin H Kim Jae-woo JW

PloS one 20121221 12

KLF8 (Krüppel-like factor 8) is a zinc-finger transcription factor known to play an essential role in the regulation of the cell cycle, apoptosis, and differentiation. However, its physiological roles and functions in adipogenesis remain unclear. In the present study, we show that KLF8 acts as a key regulator controlling adipocyte differentiation. In 3T3-L1 preadipocytes, we found that KLF8 expression was induced during differentiation, which was followed by expression of peroxisome proliferator ...[more]

PMID: 23285057

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Project description:Lung development occurs under relative hypoxia and the most important oxygen-sensitive response pathway is driven by Hypoxia Inducible Factors (HIF). HIFs are heterodimeric transcription factors of an oxygen-sensitive subunit, HIF?, and a constitutively expressed subunit, HIF1?. HIF1? and HIF2?, encoded by two separate genes, contribute to the activation of hypoxia inducible genes. A third HIF? gene, HIF3?, is subject to alternative promoter usage and splicing, leading to three major isoforms, HIF3?, NEPAS and IPAS. HIF3? gene products add to the complexity of the hypoxia response as they function as dominant negative inhibitors (IPAS) or weak transcriptional activators (HIF3?/NEPAS). Previously, we and others have shown the importance of the Hif1? and Hif2? factors in lung development, and here we investigated the role of Hif3? during pulmonary development. Therefore, HIF3? was conditionally expressed in airway epithelial cells during gestation and although HIF3? transgenic mice were born alive and appeared normal, their lungs showed clear abnormalities, including a post-pseudoglandular branching defect and a decreased number of alveoli. The HIF3? expressing lungs displayed reduced numbers of Clara cells, alveolar epithelial type I and type II cells. As a result of HIF3? expression, the level of Hif2? was reduced, but that of Hif1? was not affected. Two regulatory genes, Rar?, involved in alveologenesis, and Foxp2, a transcriptional repressor of the Clara cell specific Ccsp gene, were significantly upregulated in the HIF3? expressing lungs. In addition, aberrant basal cells were observed distally as determined by the expression of Sox2 and p63. We show that Hif3? binds a conserved HRE site in the Sox2 promoter and weakly transactivated a reporter construct containing the Sox2 promoter region. Moreover, Hif3? affected the expression of genes not typically involved in the hypoxia response, providing evidence for a novel function of Hif3? beyond the hypoxia response.

Dataset Information

Kruppel-like factor KLF8 plays a critical role in adipocyte differentiation.

Publications

Krüppel-like factor KLF8 plays a critical role in adipocyte differentiation.

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