The Gata2 repression during 3T3-L1 preadipocyte differentiation is dependent on a rapid decrease in histone acetylation in response to glucocorticoid receptor activation
The Gata2 repression during 3T3-L1 preadipocyte differentiation is dependent on a rapid decrease in histone acetylation in response to glucocorticoid receptor activation
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DOI：
10.1016/j.mce.2019.01.002
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发表时间：
2019-03-01
影响因子：
4.1
通讯作者：
Ohneda, Kinuko
中科院分区：
文献类型：
--
作者：
Ishijima, Yasushi;Ohmori, Shin'ya;Ohneda, Kinuko
转录因子GATA 2是一种抗脂肪形成因子，其表达在脂肪细胞分化过程中下调。本研究试图阐明GATA 2抑制的分子机制，发现在3 T3-L1前脂肪细胞分化过程中，GATA 2的抑制依赖于糖皮质激素受体（GR）的激活。尽管在Gata 2基因座的近端和远端区域都发现了GR的几个识别序列，但在报告基因测定中启动子活性不受GR激活的影响，并且Gata 2基因座的两个远端区域的CRISPR-Cas9介导的缺失不参与GR介导的Gata 2阻遏。值得注意的是，组蛋白乙酰化的水平显着降低在Gata 2基因座在3 T3-L1分化，和GR介导的Gata 2抑制显着缓解组蛋白去乙酰化酶抑制。这些结果表明，GR调节Gata 2基因通过减少组蛋白乙酰化在脂肪形成的早期阶段。
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.