Recent PhD from the Tjian/Darzacq group, now a Swanson Fellow at The Column Group. Happy to discuss science and company formation. Views are all my own.
Joined May 2019
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So this happened while I was vacationing. Jack and I at the @TjianDarzacq lab combined SM imaging with domain chopping (à la classical biochemistry) to determine which bits of p300 make it bind to chromatin in living cells. Turns out it's all about TF binding.
Online Now: p300 is an obligate integrator of combinatorial transcription factor inputs dlvr.it/T0l1pK
This should definitely be done with other cofactors. Many are presumed to rely on "epigenetic reader domains" for their chromatin binding, but we suspect that that may not be the case. And SM imaging is not required to test this—the correlation with FRAP is perfect.
If anyone can't access it through the above link, try this: authors.elsevier.com/a/1iL2Y…
Jonathan P. Karr retweeted
Can scientists be taught how to choose good projects?
I took a fantastic class taught by @mfgrp last quarter where the foundational hypothesis is: Yes, they can!
And I continually come back to these core insights as I think about project choice and direction in my 2nd year of PhD:
Chromatin binding capacity has been ascribed to nearly every domain of p300 at some time or other—but which is it? How does this disordered mess of a protein know where to go? We at @TjianDarzacq think we may have figured it out, at least in part.👇
biorxiv.org/content/10.1101/…
And the gist is this: p300 needs its multivalent (@PappulabWashU 👀) TF-interaction domains to bind chromatin. Integrating multiple interactions enables the protein to navigate the sea of competing TFs and CREs to find its high-affinity sites.
Many thanks to Jack, @XDarzacq, and @tgwgraham (et al.) for all their support, not only for this paper but throughout my PhD journey. Integrating multiple relationships enabled me to navigate the sea of distractions to find light at the end of the proverbial.
The “Suicide” of the Liberal Arts: Naomi Schaefer Riley interviews John Agresto wsj.com/articles/the-suicide…
Jonathan P. Karr retweeted
Excited to finally release the @biorxivpreprint of my first ever first author paper! 🚨🥳🥳🚨biorxiv.org/content/10.1101/… Any enhancer lovers in the feed!?! You know what time it is-- We're going deep! ./tweetorial.sh👇🧵
Elegant work on TF-cofactor and cofactor-promotor compatibility. This is exactly the sort of experiment needed to push our mechanistic understanding of transcription forward.
Transcription factors use a unique combination of cofactors to potentiate different promoter-dependent steps in transcription biorxiv.org/cgi/content/shor… #bioRxiv
Physical chemist 🤝 molecular biologist
⬇️
IDRs 🤝 gene regulation
So fun working with Jack Ferrie on another review (🧵) in which we challenge the canonical structure-function paradigm in TFs inherited from bacterial studies.
sciencedirect.com/science/ar…
The weakness of many IDR-based interactions allows for diverse and integrative binding modalities, making it hard to assign 1:1 relationships between interaction partners and between TFs and regulatory outcomes in isolation from the whole proteomic context.
Jonathan P. Karr retweeted
Local PhD says: Do this every day to detect protein-protein interactions using photoactivation. (Figure 6 will shock you!) 🍎🍐🥦🍊🥑
elifesciences.org/articles/7…
@tgwgraham, Jack Ferrie, Gina Dailey, @XDarzacq, @TjianDarzacq
If I were prone to confirmation bias, I might think these findings rather suggestive of a certain model.
Out now at Genes Dev "Transcriptional regulation and chromatin architecture maintenance are decoupled functions at the Sox2 locus"
genesdev.cshlp.org/cgi/conte…