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Wnt3a disrupts GR-TEAD4-PPARγ2 positive circuits and cytoskeletal rearrangement in a β-catenin-dependent manner during early adipogenesis

Title
Wnt3a disrupts GR-TEAD4-PPARγ2 positive circuits and cytoskeletal rearrangement in a β-catenin-dependent manner during early adipogenesis
Authors
Park, BongjuChang, SoojeongLee, Gwan-JunKang, ByeongsooKim, Jong KyoungPark, Hyunsung
DGIST Authors
Kim, Jong Kyoung
Issue Date
2019-01
Citation
Cell Death and Disease, 10(1)
Type
Article
Article Type
Article
ISSN
2041-4889
Abstract
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. © 2019, The Author(s).
URI
http://hdl.handle.net/20.500.11750/9532
DOI
10.1038/s41419-018-1249-7
Publisher
Nature Publishing Group
Related Researcher
  • Author Kim, Jong Kyoung Laboratory of Single-Cell Genomics
  • Research Interests Single-cell genomics, Bioinformatics, Machine Learning
Files:
Collection:
Department of New BiologyLaboratory of Single-Cell Genomics1. Journal Articles


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