Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
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The Histone Demethylase PHF2 Promotes Fat Cell Differentiation as an Epigenetic Activator of Both C/EBPα and C/EBPδ

  • Lee, Kyoung-Hwa (Ischemic/Hypoxic Disease Institute, Seoul National University College of Medicine) ;
  • Ju, Uk-Il (Departments of Biomedical Sciences, Seoul National University College of Medicine) ;
  • Song, Jung-Yup (Departments of Biomedical Sciences, Seoul National University College of Medicine) ;
  • Chun, Yang-Sook (Ischemic/Hypoxic Disease Institute, Seoul National University College of Medicine)
  • Received : 2014.06.26
  • Accepted : 2014.08.25
  • Published : 2014.10.31
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Abstract

Histone modifications on major transcription factor target genes are one of the major regulatory mechanisms controlling adipogenesis. Plant homeodomain finger 2 (PHF2) is a Jumonji domain-containing protein and is known to demethylate the histone H3K9, a repressive gene marker. To better understand the function of PHF2 in adipocyte differentiation, we constructed stable PHF2 knock-down cells by using the mouse pre-adipocyte cell line 3T3-L1. When induced with adipogenic media, PHF2 knock-down cells showed reduced lipid accumulation compared to control cells. Differential expression using a cDNA microarray revealed significant reduction of metabolic pathway genes in the PHF2 knock-down cell line after differentiation. The reduced expression of major transcription factors and adipokines was confirmed with reverse transcription- quantitative polymerase chain reaction and Western blotting. We further performed co-immunoprecipitation analysis of PHF2 with four major adipogenic transcription factors, and we found that CCATT/enhancer binding protein (C/EBP)${\alpha}$ and C/EBP${\delta}$ physically interact with PHF2. In addition, PHF2 binding to target gene promoters was confirmed with a chromatin immunoprecipitation experiment. Finally, histone H3K9 methylation markers on the PHF2-binding sequences were increased in PHF2 knock-down cells after differentiation. Together, these results demonstrate that PHF2 histone demethylase controls adipogenic gene expression during differentiation.

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References

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