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

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. •The rapid downregulation of GATA2 is mediated by GR activation in 3T3-L1 cells. (81).•GR binding to the proximal and distal regions of Gata2 is dispensable for repression. (85).•The level of H3K27 acetylation is decreased at the Gata2 locus upon GR activation. (84).