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The Gata2 repression during 3T3-L1 preadipocyte differentiation is dependent on a rapid decrease in histone

Yasushi Ishijima1, Shin'ya Ohmori1, Ai Uneme1

  • 1Department of Pharmacy, Faculty of Pharmacy, Takasaki University of Health and Welfare, Takasaki, Japan.

Molecular and Cellular Endocrinology
|January 8, 2019
PubMed
Summary

Glucocorticoid receptor (GR) represses the anti-adipogenic factor GATA2 during preadipocyte differentiation. This repression involves reduced histone acetylation at the GATA2 locus, not promoter sequence changes.

Keywords:
Adipocyte differentiationGATA2Glucocorticoid receptorHistone acetylation

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Area of Science:

  • Molecular Biology
  • Cell Biology
  • Epigenetics

Background:

  • GATA2 acts as an anti-adipogenic factor, with its expression decreasing during adipocyte differentiation.
  • The precise molecular mechanisms controlling GATA2 downregulation during adipogenesis remain incompletely understood.

Purpose of the Study:

  • To elucidate the molecular mechanisms by which GATA2 expression is repressed during 3T3-L1 preadipocyte differentiation.
  • To investigate the role of the glucocorticoid receptor (GR) in GATA2 repression.

Main Methods:

  • Reporter assays to assess promoter activity upon GR activation.
  • CRISPR-Cas9 gene editing to delete putative GR recognition sequences in the Gata2 locus.
  • Analysis of histone acetylation levels at the Gata2 locus.
  • Assessment of GATA2 repression relief by histone deacetylase inhibition.

Main Results:

  • GR activation during 3T3-L1 differentiation leads to GATA2 repression.
  • GR binding sites in the Gata2 locus and CRISPR-Cas9 deletions did not mediate this repression.
  • Histone acetylation at the Gata2 locus significantly decreased during differentiation and GR activation.
  • Histone deacetylase inhibition partially rescued GATA2 expression.

Conclusions:

  • Glucocorticoid receptor (GR) mediates GATA2 repression during early adipogenesis.
  • GR-induced GATA2 downregulation is primarily achieved through a reduction in histone acetylation at the Gata2 gene locus.
  • Epigenetic modifications, specifically histone deacetylation, play a critical role in regulating GATA2 expression during adipogenesis.