The Gata2 repression during 3T3-L1 preadipocyte differentiation is dependent on a rapid decrease in histone acetylation in response to glucocorticoid receptor activation

Yasushi Ishijima, Shin'ya Ohmori, Ai Uneme, Yusuke Aoki, Miki Kobori, Terutoshi Ohida, Momoko Arai, Misa Hosaka, Kinuko Ohneda

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

The transcription factor GATA2 is an anti-adipogenic factor whose expression is downregulated during adipocyte differentiation. The present study attempted to clarify the molecular mechanism underlying the GATA2 repression and found that the repression is dependent on the activation of the glucocorticoid receptor (GR) during 3T3-L1 preadipocyte differentiation. Although several recognition sequences for GR were found in both the proximal and distal regions of the Gata2 locus, the promoter activity was not affected by the GR activation in the reporter assays, and the CRISPR-Cas9-mediated deletion of the two distal regions of the Gata2 locus was not involved in the GR-mediated Gata2 repression. Notably, the level of histone acetylation was markedly reduced at the Gata2 locus during 3T3-L1 differentiation, and the GR-mediated Gata2 repression was significantly relieved by histone deacetylase inhibition. These results suggest that GR regulates the Gata2 gene by reducing histone acetylation in the early phase of adipogenesis.

Original languageEnglish
Pages (from-to)39-49
Number of pages11
JournalMolecular and Cellular Endocrinology
Volume483
DOIs
Publication statusPublished - 2019 Mar 1
Externally publishedYes

Keywords

  • Adipocyte differentiation
  • GATA2
  • Glucocorticoid receptor
  • Histone acetylation

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Endocrinology

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