◎ 제 270차 한림의학세미나 개최 ◎

▶ 일 시 : 2016. 11. 1(화) 17시

▶ 장 소 : 대학원의학과 세미나실(의학관 5층 3506호실)

▶ 연 자 : 박현성 교수(서울시립대학교)

▶ 주 최 : 의과대학 의과학연구소 / 세포분화 및 노화연구소 / 해부신경생물학교실

▶ 강의제목 : Wnt3a Prevents Hotspot Formation on the PPARg2 Promoter by Targeting Glucocorticoid Receptor

　Upon exposure to adipogenesis-inducing hormones, 3-isobutyl-1-methylxantine, dexamethasone and insulin (MDI), growth-arrested 3T3-L1 preadipocytes undergo two rounds of mitosis within 48 hours, then proceed to terminal differentiation. After 4 to 12 hours, C/EBPβ, glucocorticoid receptor (GR), STAT5 and other transcription factors (TF) cooperatively bind to the promoter of PPARγ gene, leading to opening of chromatin structure. Genomic region cooperatively occupied by these TFs are named ‘hotspot’. It has been studied that cannonical Wnt signaling is a key regulator which determines a lineage of mesenchymal stem cells by inhibiting adipogenesis but enhancing osteogenesis. However, inhibitory mechanism of cannonical Wnt signaling on adipogenesis is unclear. We found that early and temporal treatment of recombinant Wnt3a (5 ng/ml, first 2 days) is enough to block the induction of C/EBPα and PPARγ in 3T3-L1 cells. Wnt3a did not affect the expression of hotspot TFs, such as C/EBPβ, GR and STAT5. Instead, Wnt3a prevented C/EBPβ, GR and STAT5 from bindinghotspot on PPARγ2 promoter. Using NIH-C/β cells, which ectopically expressed C/EBPβ, we found that C/EBPβ required dexamethasone (Dex) for bindingthehotspot and Wnt3a antagonized the effects of Dex. Furthermore, microarray analysis showed that Wnt3a predominantly inhibits GR target genes in 3T3-L1 cells. These results indicated that GR binding is prerequisite for hot-spot formation and that Wnt3a prevents GR from binding to a subset of GR target genes including PPARγ2 promoter. Taken together, these data suggest that canonical Wnt3a represses adipogenesis via the inhibition of hotspotformation and chromatin opening on PPARγ2 region by targeting GR.


▶ Academic History:

1982-1986:　　BA, College of Pharmarcy, Seoul National University, Korea
1986-1988:　　MS, College of Pharmarcy, Seoul National University, Korea
1992-1997:　　Ph. D., Department of Molecular Pharmacology (Chemicals and System Biology), Stanford University, USA
1997-present: Assistant, Associate, Full Professor, Department of Life Science, University of Seoul, Korea


▶ Positions:

1997.09 – 2003.10 : Assistant Professor, Department of Life Science, University of Seoul
2003.10 – 2008.10 : Associate Professor, Department of Life Science, University of Seoul
2008.10 – present : Professor, Department of Life Science, University of Seoul


▶ Recent Main Papers published as a corresponding author:

1. Young-Kwon Park et al (2008) The Nitric Oxide Donor, SNAP, Stabilizes Trans-active Hypoxia-Inducible Factor-1α by inhibiting VHL recruitment and Asparagine Hydroxylation. Molecular Pharmacology 74(1): 236-245

2. Su Mi Choi et al. (2008) Stra13/DEC1 and DEC2 Inhibit Sterol Regulatory Element Binding Protein-1c In a Hypoxia-Inducible Factor-Dependent Mechanism. Nucleic Acids Research 36(20) 6372-6385

3. Young-Kwon Park et al. (2010) Prevention of CCAAT/enhancer binding protein β DNA binding by hypoxia during adipogenesis. J. Biol. Chem. 285(5)3289-3299

4. Ho-Youl Lee et al. (2011) Src activates HIF-1a not through direct phosphorylation of HIF-1a-specific prolyl-4 hydroxylase 2 but through activation of the NADPH oxidase/Rac pathway. Carcinogenesis 32(5) 703-712.

5. Ho-Youl Lee et al (2013) Hypoxia enhances the expression of Prostate Specific Antigen by modifying the quantity and catalytic activity of Jumonji C domain-containing histone demethylases. Carcinogenesis 34(12) 2706-2715

6. Young-Kwon Park et al. (2013) Hypoxia-Inducible Factor-2a-Dependent Hypoxic Induction of Wnt10b Expression in Adipogenic Cells. J. Biol. Chem. 288.(36) 26311-26322

7. Yunwon Moon et al (2015) Chenodeoxycholic Acid Reduces Hypoxia Inducible Factor-1α Protein and Its Target Genes. PLoS One. 10(6):e0130911.

8. Soojeong Chang et al. (2016) Hypoxic reprograming of H3K27me3 and H3K4me3 at the INK4A locus. FEBS Lett. 590(19):3407-3415.