An intrinsically disordered tug of war that fine-tunes acetylation Acetylation of histones and transcriptional regulators modulates gene expression, but how acetyltransferases define target specificity remains puzzling. In Cell Reports, Gelder et al. have shown how i...

Massive thanks to @jhenninger.bsky.social for the thoughtful preview of @katiegelder.bsky.social's recent story on CBP-IDRs. It’s fantastic to see her findings situated in the broader context of one of biology’s most dynamic fields* #IDRs #transcription #condensates www.cell.com/cell-reports...

Unstructured transcription factor interactions enable emergent specificity How intrinsically disordered regions (IDRs) influence chromatin binding and nuclear organization of transcription factors (TFs) remains unclear. We employed proximity-assisted photoactivation (PAPA), ...

While #DNAbindingdomains & #IntrinsicallyDisorderedRegions individually do not show binding specificity, "ensembles of diverse, unstructured interactions" collectively enable emergent #TranscriptionFactor specificity ➡️ www.science.org/doi/10.1126/...
#generegulation #IDRs #TFspecificity #chromatin

In its final form, the paper has evolved vastly from the original preprint. We’ve removed thousands of words and added new functional data - including a deep dissection of the complex relationship between #IDRs and lysine #acetylation. (2/7)

Redirecting

Really pleased to share the *final* version of @katiegelder.bsky.social's super work, profiling the functional roles of #IDRs in CBP. Published today 🎉

🔗https://doi.org/10.1016/j.celrep.2026.117109

#IDRs #condensates #transcription #CBP #generegulation #enhancers (1/7)

It's been a privilege to be involved with this. #FRET approaches have so many potential applications for linking in vitro studies with in cell behaviours, but lacked a consistent benchmarking molecule that works across systems: not any more! #IDRs #smFRET #singlemolecule

The suggestion is that the "state aid" regs can be unwound. But the regs creating these zones also include #IDRS and that is a murkey question mark on undoing them and cost to the country.
Also note that #BlackRock are behind a few...
So not as easy to unravel.
Posted the link in the twitter area.

Targeting the Liquid–Liquid Separation Region of c‐Maf for Treating Chromosomal Translocations in Multiple Myeloma Targeting the liquid-liquid separation region of c-Maf for treating pathogenic chromosomal translocations in multiple myeloma. c-Maf promotes cell proliferation by forming liquid–liquid phase separat....

#Article in #MedComm
Targeting the Liquid–Liquid Separation Region of c-Maf for Treating Chromosomal Translocations in Multiple Myeloma doi.org/10.1002/mco2...

#BenzoylBenzoicAcid #cMaf #ChromosomalTranslocation #LLPS #MultipleMyeloma #IDRs #BBA

Computational investigation of the sequence context of arginine/glycine-rich motifs in the human proteome - BMC Genomics Arginine-glycine (RG)-rich motifs are among the most prevalent RNA-binding elements within intrinsically disordered regions (IDRs) of proteins and play crucial roles in RNA metabolism, gene regulation, and the formation of membraneless organelles via liquid phase separation (LLPS). Despite their biological relevance and implication in neurological disorders and cancer, the sequence features and context dependencies that define functional RG motifs remain poorly characterized owing to their disordered nature and sequence variability. In this study, we present a computational framework to dissect the sequence and structural context of RG motifs across the human proteome. By contrasting a functionally defined positive dataset—enriched for RNA-binding and phase-separating proteins—with a negative dataset of RG motif proteins lacking these annotations, we identified distinct compositional and contextual signatures. RG motifs in the functionally defined positive dataset show increased enrichment of phenylalanine, tyrosine, aspartic acid, and asparagine, both within and around the motif, as well as nonrandom spatial relationships with structured RNA-binding domains. Notably, phenylalanine and tyrosine exhibit divergent positional and functional profiles, suggesting distinct mechanistic roles. Our analysis highlights the potential of sequence-based approaches to uncover functional determinants in disordered protein regions and further advances our understanding of the properties of RG motifs, offering a transferable framework for the study of other low-complexity motifs.

🖥️ New Publication Alert
Congratulations to Eric Schumbera, @dormannlab.bsky.social, @waltherlab.bsky.social & @miguelandrade66.bsky.social on their recent publication in BMC Genomics
#RGmotifs #IDRs #LLPS #HumanProteome #ComputationalMotifAnalysis
bmcgenomics.biomedcentral.com/articles/10....

New Toolset by Yale Researchers Boosts Efficacy of CAR-T Cells Targeting Blood and Solid Cancers Cancer researchers focused on improving the success of cancer immunotherapies introduced a new tool in a Yale study published Sept. 29 in Nature Chemical

Yale researchers created a new tool to improve #CARTcell therapy. Flexible protein regions called #IDRs were added to CAR-T cells—making them better at spotting and killing #cancer. yalecancercenter.org/news-article...
@nature.com #naturechemicalbiology

Top: The sequences and features of the Rim4 intrinsically disordered region (IDR) are rapidly evolving. Distribution of charged residues and RRM domains is plotted next to a phylogenetic tree of analyzed yeast species. The phylogenetic tree was built using PhytoT based on NCBI phylogenetic data and was visualized using interactive tree of life (iTOL) software [93]. RRM domains are colored light blue. Acidic residues (D, E) are colored in red and basic residues (R, K) in blue. Bottom: Schematic model showing how natural selection on the hydrophobicity of the Rim4 IDR could govern its ability to act as both a translational activator and repressor. Each function requires IDR hydrophobicity within a distinct, partially overlapping range. In Saccharomyces cerevisiae and fully complementing orthologs, hydrophobicity resides in the intersection of both optimal windows (top left). Directional selection toward one function’s optimum (top right, bottom left)—such as stronger repressor activity—shifts hydrophobicity out of the activator window and impairs that activity. Upon loss of sporulation (bottom right), selective constraints on both functions are relaxed, allowing hydrophobicity (and consequently both activities) to drift and decay.

#IntrinsicallyDisorderedRegions (IDRs) in #proteins lack stable structure & conserved sequence. This study uses cross-species rescue of yeast Rim4 to show how evolutionary pressure on #IDRs can favor biochemical traits underlying distinct functions across 100s My @plosbiology.org 🧪 plos.io/4gKBYVH

Top: The sequences and features of the Rim4 intrinsically disordered region (IDR) are rapidly evolving. Distribution of charged residues and RRM domains is plotted next to a phylogenetic tree of analyzed yeast species. The phylogenetic tree was built using PhytoT based on NCBI phylogenetic data and was visualized using interactive tree of life (iTOL) software [93]. RRM domains are colored light blue. Acidic residues (D, E) are colored in red and basic residues (R, K) in blue. Bottom: Schematic model showing how natural selection on the hydrophobicity of the Rim4 IDR could govern its ability to act as both a translational activator and repressor. Each function requires IDR hydrophobicity within a distinct, partially overlapping range. In Saccharomyces cerevisiae and fully complementing orthologs, hydrophobicity resides in the intersection of both optimal windows (top left). Directional selection toward one function’s optimum (top right, bottom left)—such as stronger repressor activity—shifts hydrophobicity out of the activator window and impairs that activity. Upon loss of sporulation (bottom right), selective constraints on both functions are relaxed, allowing hydrophobicity (and consequently both activities) to drift and decay.

#IntrinsicallyDisorderedRegions (IDRs) in #proteins lack stable structure & conserved sequence. This study uses cross-species rescue of yeast Rim4 to show how evolutionary pressure on #IDRs can favor biochemical traits underlying distinct functions across 100s My @plosbiology.org 🧪 plos.io/4gKBYVH

Top: The sequences and features of the Rim4 intrinsically disordered region (IDR) are rapidly evolving. Distribution of charged residues and RRM domains is plotted next to a phylogenetic tree of analyzed yeast species. The phylogenetic tree was built using PhytoT based on NCBI phylogenetic data and was visualized using interactive tree of life (iTOL) software [93]. RRM domains are colored light blue. Acidic residues (D, E) are colored in red and basic residues (R, K) in blue. Bottom: Schematic model showing how natural selection on the hydrophobicity of the Rim4 IDR could govern its ability to act as both a translational activator and repressor. Each function requires IDR hydrophobicity within a distinct, partially overlapping range. In Saccharomyces cerevisiae and fully complementing orthologs, hydrophobicity resides in the intersection of both optimal windows (top left). Directional selection toward one function’s optimum (top right, bottom left)—such as stronger repressor activity—shifts hydrophobicity out of the activator window and impairs that activity. Upon loss of sporulation (bottom right), selective constraints on both functions are relaxed, allowing hydrophobicity (and consequently both activities) to drift and decay.

#IntrinsicallyDisorderedRegions (IDRs) in #proteins lack stable structure & conserved sequence. This study uses cross-species rescue of yeast Rim4 to show how evolutionary pressure on #IDRs can favor biochemical traits underlying distinct functions across 100s My @plosbiology.org 🧪 plos.io/4gKBYVH

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...

Design of intrinsically disordered region binding proteins Intrinsically disordered proteins and peptides play key roles in biology, but a lack of defined structures and high variability in sequence and conformational preferences have made targeting such syst...

New approach for designing proteins that bind intrinsically disordered protein regions ➡️ www.science.org/doi/10.1126/...
#IDRs #ProteinProteinInteractions

Design of intrinsically disordered region binding proteins Intrinsically disordered proteins and peptides play key roles in biology, but a lack of defined structures and high variability in sequence and conformational preferences have made targeting such syst...

This is incredible, and going to be amazingly useful for so many things. I'm already thinking of experiments 🤔 www.science.org/doi/10.1126/... #IDRs #IDPs #ensembles

#MusicNews The International Double Reed Society faces serious threats over grants limited to under-represented groups. President Jacqueline Wilson seeks peaceful dialogue amid a divided community. Upcoming conference at Butler University aims for harmony. #IDRS #Inclusion

Tl;dr: CBP-IDRs are important! They regulate properties of CBP #ondensates to shape profiles of CBP #chromatin binding and histone acetylation.This depends on amino acid sequence, and disrupting #IDRs causes more off target CBP binding deregulates gene expression. #RNA 🧬is also important!

CBP-IDRs regulate acetylation and gene expression. Intrinsically disordered regions (IDRs) have emerged as crucial regulators of protein function, allowing proteins to sense and respond to their environment. Creb binding protein (CBP) and EP300 (p300)...

Hot off the press for your Friday morning! 🔥 Our new (and highly revised!) preprint is out. It significantly expands on our previous work, unveiling exciting new data on how CBP's intrinsically disordered regions (IDRs) regulate genes.
Link to preprint: tinyurl.com/5npjkyps

#IDRs #condensates #CBP

Intrinsically disordered regions facilitate Msn2 target search to drive promoter selectivity Transcription factors (TFs) regulate gene expression by binding specific DNA motifs, yet only a fraction of putative sites is occupied in vivo. Intrinsically disordered regions (IDRs) have emerged as ...

n/
www.biorxiv.org/content/10.1...
technion.bsky.social

#Transcription #TranscriptionFactors #IDPs #SingleMolecule #Biophysics
#IDRs #IntrinsicallyDisordered #OpticalTweezers #FacilitatedDiffusion
#DNAunzipping

Functional divergence of plant SCAR/WAVE proteins is determined by intrinsically disordered regions Intrinsically disordered regions in SCAR/WAVE proteins drive diverse functions in root hair and leaf trichome development.

Excited to share that our preprint has found a home in Science Advances. We show that intrinsically disordered regions determine the functional diversification of actin-regulatory SCAR proteins in Medicago. 🧵 1/3
www.science.org/doi/full/10....
#ScienceAdvances #PlantScience #IDRs

Finally some order in the disordered regions of proteins? 😆
#IDRs #phase_separation

#DOGE is interested in your #taxdetails folks!
The #motherlodedatabases is #IDRS, Integrated Database Systems. 60 #databases meshed into one #uber #database! Everything on a page! A #DOGE #software_engineer is being give #full access to #people’s very personal #financial info!!
This is a #WARNING‼️

Elon Musk’s DOGE team visiting FAA command center & DOGE wanting access to the Integrated Data Retrieval System which contains PRIVATE tax payer information.

#ElonMusk #DOGE #Republicans #RepublicansAreDestroyingAmerica
#FAA #IDRS #USTaxPayers

youtube.com/watch?v=TgGh...

Original post on c.im

Musk’s DOGE seeks access to personal taxpayer data, raising alarm at IRS

Under pressure from the White House, the #IRS is considering a memorandum of understanding that would give officials from #DOGE
broad access to tax-agency systems, property and datasets.

Among them is the Integrated Data […]

Original post on masto.ai

…#ElonMusk’s attacks carry a new #power since #Trump has taken office, Calo said. #Musk is a special government employee, & his #DOGE team has access to sensitive private data. As the owner of X, he can choose what content is allowed.

see earlier posted article on DOGE access of the #IRS […]

Original post on masto.ai

“#IDRS users are authorized to access only those accounts required to accomplish their official duties,” acc/to #IRS policy.
In a stmnt, WH spox said: “Waste, fraud & abuse have been deeply entrenched in our broken system for far too long. It takes direct access to the system to identify & fix […]

Original post on masto.ai

The official said the “#DOGE mission … to bring much-needed efficiency to our bureaucracy” is being carried out “legally & with the appropriate security clearances.”
A #SecurityClearance is not a sufficient credential for access to #taxpayer systems, according to #IRS procedures. #IDRS access […]

Original post on masto.ai

“The information that the #IRS has is incredibly personal. Someone w/access to it could use it & make it public…, or do something w/it, or share it w/someone…who shares it w/someone else, & your rights get violated,” Olson said.

A #Trump admin official said #DOGE personnel needed #IDRS […]

Original post on masto.ai

…it’s highly unusual to grant political appointees access to #personal #taxpayer #data, or even programs adjacent to that data…. #IRS commissioners…do not have #IDRS access. The same goes for the national taxpayer advocate, the agency’s internal consumer #watchdog, acc/to Nina Olson, who […]

Original post on masto.ai

#IDRS access is extremely limited — taxpayers who have had their info wrongfully disclosed or even inspected are entitled by #law to monetary damages — & the request for #DOGE access has raised deep concern within the #IRS….

The news comes as ~150M #taxpayers prepare to file returns by the […]