DLK2 Is a Transcriptional Target of KLF4 in the Early Stages of Adipogenesis
| Autor: | Eva M. Monsalve, José J. García-Ramírez, Jorge Laborda, Samuel Rivero, María José Díaz-Guerra |
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| Rok vydání: | 2012 |
| Předmět: |
IBMX
Transcription Genetic Phosphodiesterase Inhibitors Kruppel-Like Transcription Factors Kruppel-Like Factor 4 Mice chemistry.chemical_compound Structural Biology 1-Methyl-3-isobutylxanthine 3T3-L1 Cells Gene expression Transcriptional regulation Animals Promoter Regions Genetic Molecular Biology Transcription factor Gene knockdown Adipogenesis Chemistry Mesenchymal Stem Cells Molecular biology DLK1 Gene Expression Regulation KLF4 embryonic structures Intercellular Signaling Peptides and Proteins Protein Binding |
| Zdroj: | Journal of Molecular Biology. 417:36-50 |
| ISSN: | 0022-2836 |
| DOI: | 10.1016/j.jmb.2012.01.035 |
| Popis: | The epidermal growth factor-like protein DLK2, highly homologous to DLK1, has been identified as a modulator of adipogenesis in vitro. Knocking down Dlk2 expression prevents adipogenesis of 3T3-L1 cells but enhances that of the mesenchymal cell line C3H10T1/2. The expression of Dlk2 shows two peaks along this differentiation process: the first one, in response to 3-isobutyl-1-methylxanthine (IBMX) and dexamethasone (Dex), and the second, shortly after exposure to insulin. Nothing is known about the transcriptional regulation of Dlk2 during adipogenesis. Here, we report that, during early adipogenesis of 3T3-L1 cells, Dlk2 expression is controlled independently by IBMX and Dex. We also show that KLF4, a transcription factor critical for the control of early adipogenesis, binds directly to the Dlk2 promoter and increases Dlk2 expression in response to IBMX. Overexpression of KLF4 leads to an increase in DLK2 expression levels, whereas KLF4 knockdown downregulates the transcriptional activity of the Dlk2 promoter. Finally, we demonstrate that KLF4 regulates the basal expression of Dlk2 in C3H10T1/2 cells, and it is required for the adipogenic differentiation of those cells. These results indicate that KLF4 mediates the transcriptional regulation of Dlk2 in response to IBMX during the early stages of adipogenesis. |
| Databáze: | OpenAIRE |
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