H. Courtney Hodges

A molecular bridge helps disordered proteins work properly The findings reveal that despite their disordered nature, the protein interactions that drive gene expression are surprisingly modular and even have an underlying organization.

Drs. HC Hodges @hodgeshc.bsky.social, #chanyuensan, K Cermakova @cermakova.bsky.social et al discovered a molecular bridge that facilitates interactions among disordered proteins involved in regulating #geneExpression. #BetaCatenin @bcmhouston.bsky.social #MolecularCell blogs.bcm.edu/2025/07/24/f...

Thanks a lot!

Thanks a lot Ariel. We hope it may increase focus on IDR-domain interactions, we think there’s a lot to do in that space. Hope you’re doing great!

Thank you so much!

We were very lucky to have so many amazing collaborators on this paper, including @vaclav-veverka.bsky.social, @cermakova.bsky.social, and many others, including Yuen San Chan as first author. Please check out our paper for more information!

Excitingly, β-catenin links cBAF not only to SF-1, but also to YAP1, SOX2, FOXO3, and CBP/p300, highlighting its critical role in chromatin remodeling across diverse cellular processes

Dissection of interactions revealed that intrinsically disordered regions (IDRs) of ARID1A bind directly to the structured Armadillo domain of β-catenin

Sustained inhibition leads to loss of steroid production, positioning cBAF as a key steroidogenic dependency

We show that BAF inhibition disrupts the ability of the TF known as steroidogenic factor 1 (SF-1) and β-catenin to bind at enhancers targeted by ARID1A

How do chromatin remodelers use #IDRs to find TF binding partners? In our new Molecular Cell paper, we show that β-catenin is an adaptor that links SWI/SNF (cBAF) subunit ARID1A with binding partners via IDR-domain interactions.
www.cell.com/molecular-ce...

We also show that neural crest cells and NCC-derived neurons tolerate SWI/SNF inhibition. I anticipate that non-cycling cells are frequently independent, and cycling cells with different circuitries have alternatives or plasticity to activate Cyclin D

Thanks Hiten, it is surprising that SWI/SNF inhibition is well tolerated, and we've seen very good therapeutic window in vivo. Not all cycling cells need SWI/SNF, it's dispensable for example in HEK293Ts

What do SWI/SNF-addicted cancers have in common? And when are they most sensitive to SWI/SNF inhibition? Check out Katka’s thread highlighting our most recent paper

A labor of love - our review on why IDRs matter for cellular function is live in Nat. Rev. Mol. Cell. Biol:
www.nature.com/articles/s41...

Working with Birthe Kraglund on this was such a pleasure, and we hope this review will be helpful to a broad audience!