Barkai Lab

Systems Biology Lab
@ 🔬Weizmann Institute of Science.
# Understanding design principles of biological circuits.

[Barkai Lab @BarkaiLab]

We propose a model in which Med15 recruitment is affected by weak ABD-TF interactions and C-terminal interactions with Med2/3, leading to Med15’s UAS specificity.

[Barkai Lab @BarkaiLab]

The paradigm says that coactivators are passively recruited to targets by transcription factors (TFs). But is that the whole story?

We explore the Mediator subunit Med15 to ask: Do its activator-binding domains (ABDs) alone drive UAS targeting?
https://t.co/A3yxJXj9zj

[Barkai Lab @BarkaiLab]

Analysis of a strain deleted of 12 recruiting TFs showed that a subset of Med15 UAS specificity does not depend on recruiting TFs.

[Barkai Lab @BarkaiLab]

How do transcription factors (TFs) that recognize the same DNA motif end up binding different places in the genome? 🧬

We're excited to show you how we tackle this question in our new bioRxiv pre-print!

https://t.co/rwjTaCekCR

[Barkai Lab @BarkaiLab]

Our work suggests that TF specificity isn’t just encoded in DNA motifs or chromatin state...

Intrinsic TF features—especially disordered non-DBD regions—play a central role in determining where it binds, highlighting mechanisms beyond motif or chromatin-based models.

[Barkai Lab @BarkaiLab]

How do transcription factors (TFs) that recognize the same DNA motif end up binding different places in the genome? 🧬

We're excited to show you how we tackle this question in our new bioRxiv pre-print!

https://t.co/rwjTaCekCR

[Barkai Lab @BarkaiLab]

So what’s driving this genomic selectivity?

Our data point to disordered regions outside the DNA-binding domain as major determinants of binding strength and genomic preference, even in the absence of specific cofactors.

[Barkai Lab @BarkaiLab]

(2/8) By @JingLiu114 guided by @FJonas15 @NaamaBarkai https://t.co/6HVLJ53AF3

[Barkai Lab @BarkaiLab]

(1/8) Still wondering how low complexity intrinsically disordered regions (IDRs) guide transcription factors (TFs) to bind in genomes? Previous studies on sequence grammars; our new @MolCell paper takes the next step: de novo design of functional TF IDRs!
https://t.co/qJugw2V3qE

[Barkai Lab @BarkaiLab]

(8/8) Huge thanks to the whole Barkai lab for their support and the reviewers for their constructive feedback! And also, happy Chinese New Year! 🐎🎆

[Barkai Lab @BarkaiLab]

(7/8) We’ve moved from observing and perturbing TF IDRs to engineering them from de novo. We’re excited to exploit these grammars for synthetic biology and to see if these "simple rules" hold true across other species and protein classes! 🚀