Nutrigenomics Research Group, Faculty of Medicine, University of Tsukuba, Japan.
Department of Internal Medicine (Endocrinology and Metabolism), Faculty of Medicine, University of Tsukuba, Japan.
FEBS Lett. 2019 Feb;593(4):423-432. doi: 10.1002/1873-3468.13328. Epub 2019 Feb 1.
Glucocorticoids have various medical uses but are accompanied by side effects. The glucocorticoid receptor (GR) has been reported to regulate the clock genes, but the underlying mechanisms are incompletely understood. In this study, we focused on the suppressive effect of the GR on the expression of Rev-erbα (Nr1d1), an important component of the clock regulatory circuits. Here we show that the GR suppresses Rev-erbα expression via the formation of a complex with CLOCK and BMAL1, which binds to the E-boxes in the Nr1d1 promoter. In this GR-CLOCK-BMAL1 complex, the GR does not directly bind to DNA, which is referred to as tethering. These findings provide new insights into the role of the GR in the control of circadian rhythm.
糖皮质激素具有多种医学用途，但伴随着副作用。糖皮质激素受体（GR）已被报道调节生物钟基因，但潜在机制尚不完全清楚。在这项研究中，我们专注于 GR 对时钟调节回路重要组成部分 Rev-erbα（Nr1d1）表达的抑制作用。我们发现，GR 通过与 CLOCK 和 BMAL1 形成复合物来抑制 Rev-erbα 的表达，该复合物结合到 Nr1d1 启动子的 E 盒上。在这个 GR-CLOCK-BMAL1 复合物中，GR 并不直接与 DNA 结合，这种结合方式被称为连接。这些发现为 GR 在控制生物钟节律中的作用提供了新的见解。
