Steroid Receptors Reprogram FoxA1 Occupancy through Dynamic Chromatin Transitions.
Steroid Receptors Reprogram FoxA1 Occupancy through Dynamic Chromatin Transitions.
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DOI：
10.1016/j.cell.2016.02.067
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发表时间：
2016-04-21
期刊：
影响因子：
64.5
通讯作者：
Hager GL
中科院分区：
文献类型：
--
作者：
Swinstead EE;Miranda TB;Paakinaho V;Baek S;Goldstein I;Hawkins M;Karpova TS;Ball D;Mazza D;Lavis LD;Grimm JB;Morisaki T;Grøntved L;Presman DM;Hager GL
雌激素受体（ER）、糖皮质激素受体（GR）和叉头盒蛋白1 （FoxA1）是乳腺癌进展的重要因素。FoxA1通过其作为先锋因子的独特能力参与了内质网结合模式的建立。然而，ER、GR和FoxA1之间的分子相互作用需要进一步研究。本研究表明，ER和GR都有能力改变FoxA1先驱因子的基因组分布。活细胞中的单分子跟踪实验揭示了FoxA1与体内染色质的高度动态相互作用。此外，FoxA1因子与整个基因组中其结合位点的可检测足迹无关。这些发现支持一个模型，其中转录因子和先驱因子之间的相互作用是高度动态的。此外，在一部分基因组位点，先锋蛋白的作用可以被逆转，类固醇受体可以增强FoxA1的结合。
The estrogen receptor (ER), glucocorticoid receptor (GR), and forkhead box protein 1 (FoxA1) are significant factors in breast cancer progression. FoxA1 has been implicated in establishing ER binding patterns though its unique ability to serve as a pioneer factor. However, the molecular interplay between ER, GR, and FoxA1 requires further investigation. Here we show that ER and GR both have the ability to alter the genomic distribution of the FoxA1 pioneer factor. Single-molecule tracking experiments in live cells reveal a highly dynamic interaction of FoxA1 with chromatin in vivo. Furthermore, the FoxA1 factor is not associated with detectable footprints at its binding sites throughout the genome. These findings support a model wherein interactions between transcription factors and pioneer factors are highly dynamic. Furthermore, at a subset of genomic sites, the role of pioneer can be reversed, with the steroid receptors serving to enhance binding of FoxA1.