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Ariel Kaplan @arielkaplan.bsky.social · Jul 23

Congrats Courtney and the team! Very interesting work.

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Reposted by Ariel Kaplan

BejaLab @bejalab.bsky.social · Jun 10

Oldies but Goldies. from 2007. Light-powering Escherichia coli with proteorhodopsin www.pnas.org/doi/10.1073/...

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Reposted by Ariel Kaplan

BejaLab @bejalab.bsky.social · May 31

@arielchazan.bsky.social @galitzlil.bsky.social

BejaLab @bejalab.bsky.social · May 30

Marine Asgard Archaea’s Light-Harvesting Rhodopsin Revealed scienmag.com/marine-asgar...

Marine Asgard Archaea's Light-Harvesting Rhodopsin Revealed

In a groundbreaking advancement that challenges existing paradigms of microbial photobiology, researchers have unveiled novel structural insights into how marine Asgard archaea harness light energy.

scienmag.com

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Reposted by Ariel Kaplan

Peter Gleick @petergleick.bsky.social · May 31

There are 2 previous historical cases of countries destroying their science and universities, crippling them for decades: Lysenkoism in the USSR and Nazi Germany. The Trump administration will be the 3rd.
It's not just budgets but research, institutions, expertise, and training the next generation.

Graphs showing 25 years of budgets for the National Institute of Health, NASA, and the NSF. In all cases, the proposed budget for next year is far, far below any year of the previous quarter century.

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Reposted by Ariel Kaplan

Eric C. Greene @dnacurtain.bsky.social · May 31

open.substack.com/pub/joshuasw...

The White House Vision for Dismantling Science in One Simple Plot

Proposed NIH, NSF, and NASA budgets would be catastrophic for innovation and discovery. But they aren’t reality yet. The time to speak up is now.

open.substack.com

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Reposted by Ariel Kaplan

Maria Paz Fernandez @mariadelapax.bsky.social · May 31

www.nature.com/articles/d41...

‘Scienticide’ in Argentina sparks huge protest by researchers

Hundreds of activists wearing gas masks took to the streets to call out their government for slashing science funding.

www.nature.com

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Reposted by Ariel Kaplan

Alexis Verger 🧬🧫🧪 @alexis-verger.cpesr.fr · May 29

Nice work by the Kurumizaka Lab in @natcomms.nature.com

Multiple structures of RNA polymerase II isolated from human nuclei by ChIP-CryoEM analysis

www.nature.com/articles/s41...

Multiple structures of RNA polymerase II isolated from human nuclei by ChIP-CryoEM analysis - Nature Communications

The authors establish the ChIP-CryoEM method, which combines chromatin immunopurification coupled with cryo-electron microscopy, to visualize native human RNAPII elongation complexes in action, with a...

www.nature.com

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Reposted by Ariel Kaplan

Ariel Kaplan @arielkaplan.bsky.social · May 27

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New preprint!
How do transcription factors (TFs) use intrinsically disordered regions (IDRs) to find their target sites?

www.biorxiv.org/content/10.1...
#TranscriptionFactors #IDPs #SingleMolecule #Biophysics

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 ...

www.biorxiv.org

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Reposted by Ariel Kaplan

Pierre Bourguet @p-bourguet.bsky.social · May 28

Super cool work on the function of intrinsically disordered regions in regulating transcription factor DNA binding.

Ariel Kaplan @arielkaplan.bsky.social · May 27

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New preprint!
How do transcription factors (TFs) use intrinsically disordered regions (IDRs) to find their target sites?

www.biorxiv.org/content/10.1...
#TranscriptionFactors #IDPs #SingleMolecule #Biophysics

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 ...

www.biorxiv.org

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Reposted by Ariel Kaplan

Reuven Gordon @reuven-gordon.bsky.social · May 28

The energy landscape of a single disordered protein (tau) and the impact of PTMs is resolved. An important step to understanding the function and dysfunction of disordered proteins from their conformational ensemble. Not yet peer reviewed. www.biorxiv.org/content/10.1...

Direct observation of conformational dynamics of intrinsically disordered proteins at the single-molecule level

Intrinsically disordered proteins (IDPs) and proteins with intrinsically disordered regions (IDRs) are integral to many biological processes, including neurotransmitter regulation, microtubule regulat...

www.biorxiv.org

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Reposted by Ariel Kaplan

Daniel Ibrahim @danielibrahim.bsky.social · May 27

How to find Evolutionary Conserved Enhancers in 2025? 🐣-🐭
Check out our paper - fresh off the press!!!
We find widespread functional conservation of enhancers in absence of sequence homology
Including: a bioinformatic tool to map sequence-diverged enhancers!
rdcu.be/enVDN
github.com/tobiaszehnde...

Conservation of regulatory elements with highly diverged sequences across large evolutionary distances

Nature Genetics - Combining functional genomic data from mouse and chicken with a synteny-based strategy identifies positionally conserved cis-regulatory elements in the absence of direct sequence...

rdcu.be

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Ariel Kaplan @arielkaplan.bsky.social · May 28

Thanks!

Ariel Kaplan @arielkaplan.bsky.social · May 28

Thanks!
We don't know specifically about the sliding length - but that's definitely something we would like to look at.
And thank you for reminding me about your paper, very relevant and interesting.

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Ariel Kaplan @arielkaplan.bsky.social · May 27

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

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

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 ...

www.biorxiv.org

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Ariel Kaplan @arielkaplan.bsky.social · May 27

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Kudos to Nir Strugo (nirstrugo.bsky.social)‬ who led the work, with help from Carmit Burstein, Noam Nago, and Hadeel Khamis, and also Saddam Hossein from the Hoffman Lab.
Thanks to Hagen Hofmann, Naama Barkai, Moshe Goldsmith, Gabi Rosenblum and vmindel.bsky.social�� for comments and/or help!

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Ariel Kaplan @arielkaplan.bsky.social · May 27

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Bottom line:
Using single-molecule assays, we show that IDRs modulate Msn2 binding to its target motif by tuning genome exploration.
This occurs via non-specific (or rather quasi-specific) association and sequence-sensitive facilitated diffusion, shaped by disordered regions.

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Ariel Kaplan @arielkaplan.bsky.social · May 27

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Together, our results support a model in which IDRs:
1. Facilitate initial non-specific association, stabilized by the DBD. Association, stabilization, or both, are sensitive to the sequence.
2. Enhance sequence-dependent diffusion toward the motif.

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Ariel Kaplan @arielkaplan.bsky.social · May 27

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What about the diffusion? sequence-sensitive ?
We perturbed IDR function during the sliding phase only (post-binding).
This had no effect for the arb. seq. but reduced STO probability and delayed detection for Hap4
⇒ IDRs enhance diffusion in a sequence-sensitive manner.

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Ariel Kaplan @arielkaplan.bsky.social · May 27

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Can we pinpoint which specific phase of the search is sequence-sensitive?
Hap4 showed increased non-specific binding, while dissociation rates (very low for both environments) were similar.
Conclusion: initial association, but not dissociation, is sequence-sensitive.

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Ariel Kaplan @arielkaplan.bsky.social · May 27

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Can this mechanism explain Msn2’s promoter selectivity?
We tested by replacing our "arbitrary" flanking region with a segment from the Hap4 promoter (a native Msn2 target).
Strikingly, STO binding increased to ~100%, and TFs were detected faster.

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Ariel Kaplan @arielkaplan.bsky.social · May 27

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Surprisingly, TFs were detected at the motif in ~30% of molecules, despite no free TFs in solution and irreversible dissociation conditions. This required intact IDRs, supporting a search mechanism based on non-specific binding and 1D diffusion on DNA.

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Ariel Kaplan @arielkaplan.bsky.social · May 27

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To test this, we developed a new assay, which we called Sliding-to-Target Occupation (STO):
We unzip DNA, incubate with TFs for 1 min, and then move to a TF-free channel where we perform repeated unzipping cycles to detect binding at the motif.

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Ariel Kaplan @arielkaplan.bsky.social · May 27

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Since IDRs increased both non-specific binding and association to the motif, we asked:
Can these non-specifically bound proteins ultimately reach the motif by sliding on DNA?

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Ariel Kaplan @arielkaplan.bsky.social · May 27

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We also found that Msn2 interacts with single-stranded DNA through its IDRs. This was evident in rezipping hysteresis, EMSA, and the kinetics of DNA hairpin closing.
These interactions may be relevant for binding melted promoter regions during activation.

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Ariel Kaplan @arielkaplan.bsky.social · May 27

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Based on these assays, and complementary EMSA and mass photometry experiments, we could conclude that IDRs promote cooperative formation of non-specific multimeric Msn2–DNA complexes, which are further stabilized by the DBD.

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