Wnt3a disrupts GR-TEAD4-PPARγ2 positive circuits and cytoskeletal rearrangement in a β-catenin-dependent manner during early adipogenesis
| Autor: | Gwan-Jun Lee, Bongju Park, Hyunsung Park, Byeongsoo Kang, Soojeong Chang, Jong Kyoung Kim |
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| Rok vydání: | 2018 |
| Předmět: |
Cancer Research
Immunology Muscle Proteins Transfection Article 03 medical and health sciences Cellular and Molecular Neuroscience Mice 0302 clinical medicine Glucocorticoid receptor Receptors Glucocorticoid 3T3-L1 Cells Wnt3A Protein Adipocytes Animals Humans TEAD4 lcsh:QH573-671 Cytoskeleton Promoter Regions Genetic Transcription factor beta Catenin 030304 developmental biology 0303 health sciences Adipogenesis lcsh:Cytology Chemistry CCAAT-Enhancer-Binding Protein-beta HEK 293 cells TEA Domain Transcription Factors Cell Biology Chromatin Cell biology DNA-Binding Proteins PPAR gamma HEK293 Cells NIH 3T3 Cells 030217 neurology & neurosurgery WNT3A Transcription Factors |
| Zdroj: | Cell Death & Disease Cell Death and Disease, Vol 10, Iss 1, Pp 1-16 (2019) |
| ISSN: | 2041-4889 |
| Popis: | Adipogenesis is a process which induces or represses many genes in a way to drive irreversible changes of cell phenotypes; lipid accumulation, round cell-shape, secreting many adipokines. As a master transcription factor (TF), PPARγ2 induces several target genes to orchestrate these adipogenic changes. Thus induction of Pparg2 gene is tightly regulated by many adipogenic and also anti-adipogenic factors. Four hours after the treatment of adipogenic hormones, more than fifteen TFs including glucocorticoid receptor (GR), C/EBPβ and AP-1 cooperatively bind the promoter of Pparg2 gene covering 400 bps, termed “hotspot”. In this study, we show that TEA domain family transcription factor (TEAD)4 reinforces occupancy of both GR and C/EBPβ on the hotspot of Pparg2 during early adipogenesis. Our findings that TEAD4 requires GR for its expression and for the ability to bind its own promoter and the hotspot region of Pparg2 gene indicate that GR is a common component of two positive circuits, which regulates the expression of both Tead4 and Pparg2. Wnt3a disrupts these mutually related positive circuits by limiting the nuclear location of GR in a β-catenin dependent manner. The antagonistic effects of β-catenin extend to cytoskeletal remodeling during the early phase of adipogenesis. GR is necessary for the rearrangements of both cytoskeleton and chromatin of Pparg2, whereas Wnt3a inhibits both processes in a β-catenin-dependent manner. Our results suggest that hotspot formation during early adipogenesis is related to cytoskeletal remodeling, which is regulated by the antagonistic action of GR and β-catenin, and that Wnt3a reinforces β-catenin function. |
| Databáze: | OpenAIRE |
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