Histone methylation regulator PTIP is required for PPARgamma and C/EBPalpha expression and adipogenesis

Young-Wook Cho1, SunHwa Hong, Qihuang Jin

  • 1Nuclear Receptor Biology Section, CEB, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.

Cell Metabolism
|July 9, 2009
PubMed

Insights

PTIP protein is crucial for adipogenesis, regulating key genes PPARgamma and C/EBPalpha. Its absence impairs fat cell development and brown adipose tissue weight, highlighting its essential role.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Epigenetics

Background:

  • Adipogenesis, or fat cell differentiation, is a complex process controlled by transcription factors like PPARgamma and C/EBPalpha.
  • The precise regulatory mechanisms governing PPARgamma and C/EBPalpha expression during adipogenesis are not fully understood.

Purpose of the Study:

  • To investigate the role of PTIP (protein interacting with ТHРS) in regulating PPARgamma and C/EBPalpha expression and its impact on adipogenesis.

Main Methods:

  • Utilized mouse embryonic fibroblasts (MEFs) and preadipocytes, including PTIP-deficient models.
  • Assessed gene expression of PPARgamma and C/EBPalpha via quantitative PCR and Western blotting.
  • Analyzed histone modifications (H3K4 trimethylation) and RNA polymerase II enrichment at target gene promoters using ChIP-qPCR.
  • Evaluated adipogenesis by measuring lipid accumulation and observing morphological changes.
  • Examined the effect of PTIP deletion on brown adipose tissue weight in vivo.

Main Results:

  • PTIP deletion in MEFs significantly reduced PPARgamma expression and C/EBPalpha expression stimulated by PPARgamma.
  • PTIP is essential for the induction of PPARgamma and C/EBPalpha during preadipocyte differentiation.
  • PTIP deficiency led to decreased H3K4 trimethylation and RNA polymerase II recruitment on PPARgamma and C/EBPalpha promoters.
  • PTIP(-/-) MEFs and preadipocytes exhibited severe defects in adipogenesis, which were rescued by co-expressing PPARgamma and C/EBPalpha.
  • PTIP deletion in brown adipose tissue resulted in a significant reduction in tissue weight.

Conclusions:

  • PTIP plays a critical role in adipogenesis by regulating the expression of PPARgamma and C/EBPalpha.
  • PTIP influences adipogenesis through epigenetic mechanisms involving H3K4 trimethylation and RNA polymerase II recruitment.
  • PTIP is essential for both white and brown adipose tissue development.

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