Voss Ty C, Hager Gordon L
Laboratory of Receptor Biology and Gene Expression, Building 41, B602, 41 Library Drive, National Cancer Institute, NIH Bethesda, MD 20892-5055, USA.
Biochim Biophys Acta. 2008 Nov;1783(11):2044-51. doi: 10.1016/j.bbamcr.2008.06.022. Epub 2008 Jul 16.
Chromatin and associated regulatory proteins regulate gene expression in the natural environment of the intact cell nucleus. Specific combinations of DNA-binding transcription factors and recruited coregulatory proteins alter the conformation of chromatin at promoters and enhancers of target genes to stimulate or repress transcription. The dynamic nature of the regulatory proteins active in these processes allows the cell to modulate gene expression very rapidly, an important feature in many physiological processes. Live cell imaging and photobleaching studies of fluorescently-tagged proteins reveal that many transcription factors and other chromatin-associated proteins rapidly move through the nucleoplasm. Transcription factors also transiently interact with specific regulatory sequences in chromatin, suggesting that gene activation does not require the formation of stable long-lived regulatory complexes on the chromatin. In this review we discuss how dynamic interactions allow transcriptional regulatory proteins find their targets within the nucleus, alter target chromatin structure, and modulate physiological gene expression.
染色质及相关调控蛋白在完整细胞核的自然环境中调节基因表达。DNA结合转录因子与募集的共调控蛋白的特定组合改变了靶基因启动子和增强子处染色质的构象，从而刺激或抑制转录。参与这些过程的调控蛋白的动态性质使细胞能够非常迅速地调节基因表达，这是许多生理过程中的一个重要特征。对荧光标记蛋白的活细胞成像和光漂白研究表明，许多转录因子和其他染色质相关蛋白在核质中快速移动。转录因子还与染色质中的特定调控序列瞬时相互作用，这表明基因激活并不需要在染色质上形成稳定的长寿调控复合物。在本综述中，我们讨论了动态相互作用如何使转录调控蛋白在细胞核内找到其靶标、改变靶标染色质结构并调节生理基因表达。
