Pascal Bielefeld, Marijn Schouten, Paul J Lucassen, Carlos P Fitzsimons
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引用次数: 8
摘要
糖皮质激素的自然振荡诱导糖皮质激素受体(GR)的循环激活,这是一种具有良好特征的配体激活转录因子。这些GR激活/失活的循环导致基因组应答元件的快速GR交换和GR通过伴侣机制的再循环,最终产生GR介导的靶基因转录活性脉冲。在最近的一篇文章中,我们讨论了昼夜节律和高频(超高频)糖皮质激素振荡对海马神经干/祖细胞(NSPCs)基因表达动态控制的影响(Fitzsimons et al., Front。Neuroendocrinol。, 2016)。有趣的是,这种振荡转录活性在其他转录因子中也很常见,其中许多转录因子调节NSPCs的关键生物学功能,如NF-kB、p53、Wnt和Notch。在这里,我们讨论了这些转录因子的振荡行为,它们在生物学上精确的靶调控中的作用,以及在NSPCs中转录活性和基因表达的动态控制中的潜在重要性。
Transcription factor oscillations in neural stem cells: Implications for accurate control of gene expression.
Naturally occurring oscillations in glucocorticoids induce a cyclic activation of the glucocorticoid receptor (GR), a well-characterized ligand-activated transcription factor. These cycles of GR activation/deactivation result in rapid GR exchange at genomic response elements and GR recycling through the chaperone machinery, ultimately generating pulses of GR-mediated transcriptional activity of target genes. In a recent article we have discussed the implications of circadian and high-frequency (ultradian) glucocorticoid oscillations for the dynamic control of gene expression in hippocampal neural stem/progenitor cells (NSPCs) (Fitzsimons et al., Front. Neuroendocrinol., 2016). Interestingly, this oscillatory transcriptional activity is common to other transcription factors, many of which regulate key biological functions in NSPCs, such as NF-kB, p53, Wnt and Notch. Here, we discuss the oscillatory behavior of these transcription factors, their role in a biologically accurate target regulation and the potential importance for a dynamic control of transcription activity and gene expression in NSPCs.