کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2818416 | 1569860 | 2011 | 11 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: High content imaging-based assay to classify estrogen receptor-α ligands based on defined mechanistic outcomes High content imaging-based assay to classify estrogen receptor-α ligands based on defined mechanistic outcomes](/preview/png/2818416.png)
Estrogen receptor-α (ER) is an important target both for therapeutic compounds and endocrine disrupting chemicals (EDCs); however, the mechanisms involved in chemical modulation of regulating ER transcriptional activity are inadequately understood. Here, we report the development of a high content analysis-based assay to describe ER activity that uniquely exploits a microscopically visible multi-copy integration of an ER-regulated promoter. Through automated single-cell analyses, we simultaneously quantified promoter occupancy, recruitment of transcriptional cofactors and large-scale chromatin changes in response to a panel of ER ligands and EDCs. Image-derived multi-parametric data was used to classify a panel of ligand responses at high resolution. We propose this system as a novel technology providing new mechanistic insights into EDC activities in a manner useful for both basic mechanistic studies and drug testing.
Journal: Gene - Volume 477, Issues 1–2, 15 May 2011, Pages 42–52