High content imaging-based assay to classify estrogen receptor-α ligands based on defined mechanistic outcomes.
Gene
; 477(1-2): 42-52, 2011 May 15.
Article
in En
| MEDLINE
| ID: mdl-21256200
ABSTRACT
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Green Fluorescent Proteins
/
Estrogen Receptor alpha
/
Microscopy, Fluorescence
Limits:
Humans
Language:
En
Journal:
Gene
Year:
2011
Document type:
Article
Affiliation country: