Endocrine disrupting chemicals differentially alter intranuclear dynamics and transcriptional activation of estrogen receptor-α

• Published in: iScience Vol. 24; no. 11; p. 103227
• Main Authors: Bolt, Michael J., Singh, Pankaj, Obkirchner, Caroline E., Powell, Reid T., Mancini, Maureen G., Szafran, Adam T., Stossi, Fabio, Mancini, Michael A.
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 19.11.2021; Elsevier
• Subjects: Biological sciences; Biophysical Chemistry; Cell biology; Cell biology; Biophysical Chemistry; Biological sciences
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2021.103227

Transcription is a highly regulated sequence of stochastic processes utilizing many regulators, including nuclear receptors (NR) that respond to stimuli. Endocrine disrupting chemicals (EDCs) in the environment can compete with natural ligands for nuclear receptors to alter transcription. As nuclear dynamics can be tightly linked to transcription, it is important to determine how EDCs affect NR mobility. We use an EPA-assembled set of 45 estrogen receptor-α (ERα) ligands and EDCs in our engineered PRL-Array model to characterize their effect upon transcription using fluorescence in situ hybridization and fluorescence recovery after photobleaching (FRAP). We identified 36 compounds that target ERα-GFP to a transcriptionally active, visible locus. Using a novel method for multi-region FRAP analysis we find a strong negative correlation between ERα mobility and inverse agonists. Our findings indicate that ERα mobility is not solely tied to transcription but affected highly by the chemical class binding the receptor. [Display omitted] •Development of a new algorithm for multi-foci FRAP analysis•ERα agonists can be segregated into fast-moving and slow-moving receptor groups•ERα inverse agonists receptor mobility inversely correlates with transcription•Steroidal compounds result in a slower moving receptor than other classes Biological sciences; Cell biology; Biophysical Chemistry