Okada Maiko, Takezawa Shin-ichiro, Mezaki Yoshihiro, Yamaoka Ikuko, Takada Ichiro, Kitagawa Hirochika, Kato Shigeaki
The Institute of Molecular and Cellular Biosciences, University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.
EMBO Rep. 2008 Jun;9(6):563-8. doi: 10.1038/embor.2008.55. Epub 2008 May 2.
The female sex steroid hormone oestrogen stimulates both cell proliferation and cell differentiation in target tissues. These biological actions are mediated primarily through nuclear oestrogen receptors (ERs). The ligand-dependent transactivation of ERs requires several nuclear co-regulator complexes; however, the cell-cycle-dependent associations of these complexes are poorly understood. By using a synchronization system, we found that the transactivation function of ERalpha at G2/M was lowered. Biochemical approaches showed that ERalpha associated with two discrete classes of ATP-dependent chromatin-remodelling complex in a cell-cycle-dependent manner. The components of the NuRD-type complex were identified as G2/M-phase-specific ERalpha co-repressors. Thus, our results indicate that the transactivation function of ERalpha is cell-cycle dependent and is coupled with a cell-cycle-dependent association of chromatin-remodelling complexes.
雌性甾体激素雌激素可刺激靶组织中的细胞增殖和细胞分化。这些生物学作用主要通过核雌激素受体(ERs)介导。ERs的配体依赖性反式激活需要几种核共调节复合物;然而,这些复合物的细胞周期依赖性关联却知之甚少。通过使用同步系统,我们发现ERα在G2/M期的反式激活功能降低。生化方法表明,ERα以细胞周期依赖性方式与两类不同的ATP依赖性染色质重塑复合物相关联。NuRD型复合物的成分被鉴定为G2/M期特异性ERα共抑制因子。因此,我们的结果表明,ERα的反式激活功能是细胞周期依赖性的,并且与染色质重塑复合物的细胞周期依赖性关联相关。