Abstract
Steroid hormone receptors are ligand-binding transcription factors essential for mammalian physiology. The androgen receptor (AR) binds androgens mediating gene expression for sexual, somatic and behavioural functions, and is involved in various conditions including androgen insensitivity syndrome and prostate cancer1. Here we identified functional mutations in the formin and actin nucleator DAAM2 in patients with androgen insensitivity syndrome. DAAM2 was enriched in the nucleus, where its localization correlated with that of the AR to form actin-dependent transcriptional droplets in response to dihydrotestosterone. DAAM2 AR droplets ranged from 0.02 to 0.06 µm3 in size and associated with active RNA polymerase II. DAAM2 polymerized actin directly at the AR to promote droplet coalescence in a highly dynamic manner, and nuclear actin polymerization is required for prostate-specific antigen expression in cancer cells. Our data uncover signal-regulated nuclear actin assembly at a steroid hormone receptor necessary for transcription.
| Original language | English |
|---|---|
| Journal | Nature |
| Volume | 617 |
| Issue number | 7961 |
| Pages (from-to) | 616-622 |
| Number of pages | 7 |
| ISSN | 0028-0836 |
| DOIs | |
| Publication status | Published - 18.05.2023 |
Funding
We thank B. Karwelies and P. Davarnia for technical support; laboratory members of the Grosse group for discussions; O. Wunderlich for technical assistance; J. Altmueller for help with the sequencing facility; and H. U. Schweikert for providing GSFs. The study has been funded by the German Research Council (Deutsche Forschungsgemeinschaft) to N.C.H. (nos. HO 6028/2-1 and HO 6028/3-1) and R.G. (no. GR2111/13-1) and under Germany’s Excellence Strategy (EXC-2189, project ID: 390939984).
Research Areas and Centers
- Research Area: Medical Genetics
DFG Research Classification Scheme
- 2.22-03 Human Genetics
