Too many people to thank, but all this journey would not have been possible without the mentorship of Adali Pecci, Valeria Levi, the Gordon Hager lab, and crucial collaborations with the Estébanez-Perpiñá team, who joined us in this fight.
Special thanks to my PhD student, Agustina!
In summary
- GR is mostly dimeric upon ligand activation
- GR’s final conformation might be a tetramer
- GR-GR contacts depend on a complex, intertwined crosstalk within all structural domains: LBD, DBD, and likely the NTD
- Is transrepression necessary to explain GR action?
Finally, Eva and Pablo’s team were able to crystallize GR’s LBD in a tetrameric form, giving us a unique opportunity to probe and test different oligomerization surfaces on GR. They even managed to capture GR tetramers in vitro with a GR DBD-LBD fragment!
doi.org/10.1093/nar/...
By combing X-ray crystallography and live cell studies, Alba and Andrea were able to find new surfaces of GR-GR contacts, suggesting that several types of dimers can coexist in the cell
What was really missing, even though we already had live-cell experimental data, was the crystal structure of the tetramer. Here comes Eva and Pablo to the rescue!
The idea that GR is a tetramer was received with high skepticism, to put it mildly, even though we demonstrated increased transcriptional activity for a constitutive tetrameric mutant receptor (GRtetra),
www.genome.org/cgi/doi/10.1...
Back in 2016, we were able to quantify the oligomeric state of GR on a tandem array of DNA elements inside live cells, and we were shocked to find out that GR was actually a tetramer when bound to chromatin!
doi.org/10.1073/pnas...
Fast forward to 2021, we also found that a mostly monomeric GR mutant (GRmon) was unable to activate genes and bind to chromatin, suggesting that most of GR activity was done by GR dimers
dx.doi.org/10.1038/s414...
By 2014, we confirmed that the GRdim mutant, allegedly monomeric and thus the main evidential basis for the claim of monomeric GR action, was actually a dimer. Where are all the monomers?
doi.org/10.1371/jour...
In 2010, we applied the N&B assay to quantify, for the first time, the oligomeric state of GR in live cells. Surprisingly, we find that the population of GR is mostly dimeric in the nucleus. Where are all the monomers?
doi.org/10.1371/jour...
This paper marks the culmination of a 15-year (and 7 papers) journey to challenge #Glucocorticoid-Receptor(GR) dogma. The classic paradigm of GR action states that monomeric GR and dimeric GR regulate a different set of genes
Happy to share the latest publication led by Pablo Fuentes-Prior, G. Hager, and @estebanezlab.bsky.social, with talented co-first authors Andrea, Alba, and Agustina.
This one feels special to me, as I explain in this thread below....
Dear colleagues,
Science in Argentina is under siege. Government funding has stopped and the system is about to collapse.
Please help us spread the word to stop the exodus of our best human resources.
youtu.be/76tYd-QRIfI?...
www.nature.com/articles/d41...
Our new paper is out in iScience. Congratulations for Belen! We have found new evidence that supports the involvement of glucocorticoid receptor condensates in transcription control.
Happy to share that our manuscript has been accepted in iScience!
www.cell.com/iscience/ful...
Go check it out to find out whether glucocorticoid receptor condensates have a role in transcriptional regulation...
Thank you for making our review article on the top 20 downloads @commsbio.bsky.social !
Don´t miss the chance to keep growing your endless pdfs folder
www.nature.com/articles/s42...
Interested in learning what fluorescence fluctuations tools can teach us about transcription factor action in live cells? Check out our new review where we focus on the glucocorticoid receptor as a model transcription factor for this kind of techniques, including N&B, FCS and FCCS.
Happy to share our latest review on Glucocorticoid Receptor as seen under the lens of fluorescence fluctuation techniques!
www.sciencedirect.com/science/arti...
A must read for parents, educators, politicians, and everyone in between. Highly recommended!
Gracias Pablo!
New Preprint!
Multidisplinary approach to unravel the complex quaternary structure of the glucocorticoid receptor.
www.biorxiv.org/content/10.1...
Pre-print Alert! 🚨
Do Glucocorticoid receptor (GR) condensates have a role in transcription?
Check out our latest work in collaboration with Valeria Levi´s lab and talented PhD student Belén Benitez.
doi.org/10.1101/2024...