Nuclear myosin I mediates genomic clustering of estrogen receptor-α without affecting ligand-induced transcriptional robustness
Swaminathan, S.; Pandith, I. A.; Mann, R.; Soota, D.; Najar, A. H.; Notani, D.
Show abstract
Ligand-induced transcriptional responses are rapid and robust. Estrogen, one such ligand, exerts its rapid effects through the steroid hormone receptor estrogen receptor-alpha (ER). Upon stimulation, ER binds to clustered enhancers to drive target gene expression. Here, we identify nuclear myosin 1 (NM1/Myo1c) as a positive regulator of ER clustering on enhancers, promoting condensate formation on chromatin. NM1 is enriched on chromatin at the peak of the signaling response, and its depletion leads to a genome-wide reduction in ER occupancy and condensates. Surprisingly, these alterations in chromatin occupancy of ER have minimal impact on estrogen-regulated gene expression, suggesting that transcriptional output remains robust despite disruptions in transcription factor clustering. This study reveals a regulatory axis between Myo1c and ER clustering, offering fresh insights into the intricacies of transcriptional regulation.
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