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Posts by Dr. Sedona Murphy

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Synthetic chromosomes for 3D functional genomics: from principles to AI-guided design The role of genome 3D organization for fundamental chromatin processes, such as long-range promoter-activator regulatory interactions, remains ambiguo…

Happy to share our review of the past, recent, and future applications of synthetic genomics in studying the 3D functional organization of chromosomes, a set of approaches that are gaining momentum!

www.sciencedirect.com/science/arti...

5 days ago 19 14 0 0
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Our H1 paper is out #ScienceAdvances:
www.science.org/doi/10.1126/...
@masaashimazoe.bsky.social et al. reveal that linker histone H1 acts as a liquid-like glue to organize chromatin in live cells. πŸŽ‰ Fantastic collab with @rcollepardo.bsky.social @janhuemar.bsky.social and othersβ€”huge thanks! πŸ™Œ 1/

1 week ago 60 29 2 4
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Mosaic gastruloids reveal a temporal restriction for developmental cell competition - Nature Cell Biology Frenster et al. utilize mosaic mouse gastruloids as a model of cell fitness and competition, identifying a temporal window between primed pluripotency and early gastrulation during which cell competit...

πŸ₯³ I am happy to share our latest manuscript published in @natcellbio.nature.com We use #Gastruloids to study #CellCompetition during early mammalian development and find not only that this is highly pronounced in our system but also tightly restricted in time. (1/12) www.nature.com/articles/s41...

2 weeks ago 69 22 6 0
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Please check out our newest work on fluorogenic speed imager probes, in which we combine the strengths of speed-optimized imagers and fluorogenic imagers.

#SuperResolution #DNAPAINT #microscopy

www.biorxiv.org/content/10.6...

3 weeks ago 33 11 0 1
Embryonic stem cell factors DPPA2/4 amplify active H3K4me3–H2AK119ub chromatin domains in non-small cell lung cancer A biweekly scientific journal publishing high-quality research in molecular biology and genetics, cancer biology, biochemistry, and related fields

Delighted to share the lab's latest led by superstar Janith and funded by @snowmedical.bsky.social.
What happens when embryonic factors are reawakened in cancers? We uncovered how DPPA2/4 amplify chromatin states in non-small cell lung cancer πŸ§¬πŸ”¬πŸ§ͺ
genesdev.cshlp.org/content/earl...
Tutorial πŸ‘‡ (1/8)

4 weeks ago 28 15 1 0
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At #EMBLTranscript, experts will share breakthroughs across the full spectrum of #transcription – from cis-regulatory function and long-range regulation to 3D looping, basal transcriptional machinery, #chromatin modifications, #epigenetic inheritance, and more 🧬

Join us: s.embl.org/trm26-01-bl

1 month ago 15 9 1 1

New preprint from our lab... We applied our hopping technology to relocate CTCF binding sites to thousands of alternative positions in the Sox2 locus: www.biorxiv.org/content/10.6...

1 month ago 42 17 0 0

Interallelic cis-regulatory dominance promotes robustness and evolutionary innovation www.biorxiv.org/content/10.64898/2026.03...

1 month ago 9 5 0 1
A dual role for CTCF in development CTCF is an essential DNA binding protein whose absence leads to embryonic lethality. CTCF is primarily known for its role in 3D genome organization where its N-terminal domain interacts with cohesin to anchor chromatin loops. How CTCF facilitates proper embryonic development remains unclear, necessitating temporal control to resolve its stage-specific functions. By combining gastruloids, an in vitro model of embryonic development, with a degron system to rapidly deplete CTCF at defined timepoints, we show that early CTCF depletion impairs early gastruloid morphogenesis. Surprisingly, ATAC-seq and time-resolved RNA-seq revealed that differentiation was unaffected. CTCF binding is strongly enriched at promoters of downregulated genes. Re-expression of a CTCF variant with an N-terminal truncation, incapable of looping, was sufficient to rescue the expression of CTCF-promoter bound genes and the defects in morphogenesis. However, extended culture (up to 168 hours) of gastruloids reconstituted with N-terminal truncated CTCF led to their collapse. Our work shows that CTCF has a dual function in early mammalian development: at early stages CTCF regulates developmentally important genes through promoter binding, while at later stages its looping function is required for correct development. ### Competing Interest Statement The authors have declared no competing interest. European Research Council, https://ror.org/0472cxd90, 637587, 865459 Dutch Research Council, https://ror.org/04jsz6e67, 016.161.316, VI.C.222.049 Dutch Cancer Society, https://ror.org/0368jnd28, N/A

🧡 CTCF is essential for embryonic development, but why has remained unclear. By combining gastruloids with a temporal degron system, we uncovered a surprising dual function β€” and it changes how we think about CTCF's role in development. 1/8 www.biorxiv.org/content/10.6...

1 month ago 112 55 7 4
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How do pairs of DNA loci - such as enhancers and promoters - find each other inside the nucleus? πŸ€”

Most models assume the random forces driving locus motion are independent in space

New preprint by
@janniharju.bsky.social: this assumption fails in living cells 🧡

www.biorxiv.org/content/10.6...

1 month ago 113 46 3 1

Very happy to have contributed to this mastodon of a paper by Yinan @yinanwan.bsky.social. Whole-mount spatial transcriptomics in zebrafish y'all 🐟πŸ§ͺ

1 month ago 178 26 13 1
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Whole-embryo spatial transcriptomics at subcellular resolution from gastrulation to organogenesis Gene expression patterns underlie development, but their systematic detection in whole embryos has remained elusive. We introduce a whole-embryo imaging platform using multiplexed error-robust fluores...

Very happy to see this out. πŸ‘ @yinanwan.bsky.social
Bogdan Bintu and team.
Whole-embryo spatial transcriptomics at subcellular resolution from gastrulation to organogenesis | free link Science www.science.org/eprint/5MHTM...

1 month ago 181 77 6 8

Ever wondered how a eukaryotic transcription factor finds its specific DNA motif in the vast genome? In this preprint, we directly measured the dynamics of this search process in living cells, revealing a cooperative mechanism mediated by disordered regions. 1/10 doi.org/10.64898/202...

1 month ago 95 40 1 2
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I started Awesome Life Science Resources: a curated list of resources on work culture, career, and communication for life scientists. Built for PhD students, postdocs, and PIs.

Check it out:
github.com/jjfroehlich/...

1 month ago 45 21 3 4
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Accessory subunits of PRC2 mimic H3K27me3 to restrict the spread of Polycomb domains Some proteins mimic the repressive mark H3K27me3, but the physiological relevance of this phenomenon was unclear. Agius et al. show that the PRC2 subunits JARID2 and PALI1 mimic H3K27me3 to antagonize...

1/ 🧡 In our new paper, we show that JARID2 and PALI1 mimic H3K27me3 to antagonise PRC2. www.cell.com/molecular-ce...

1 month ago 59 25 1 2
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Decoding the molecular logic of rapidly evolving ZAD zinc finger proteins in Drosophila Identification of ZAD-ZnF genes as key regulators of genome organization during Drosophila embryogenesis.

Diving into evolutionary biology! What is the origin of the most abundant class of insect transcription factors, ZAD-ZnFs? We suggest that they evolved from ancestral insulator-binding proteins that control 3D genome topology.

www.science.org/doi/10.1126/...

1 month ago 33 15 0 0
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Post-replicative chromatin accessibility predicts cell fate change Knudsen and colleagues use repli-ATAC-seq to compare replicated and unreplicated chromatin in two models of cell identity change. They find that lineage-specific elements are accessible earlier in rep...

DNA replication globally disrupts the epigenome. But does this create a chromatin-access opportunity for TF binding to facilitate cell identity change? Now 𝐫𝐞𝐩π₯𝐒-𝐀𝐓𝐀𝐂-𝐬𝐞πͺ shows π˜₯𝘦 𝘯𝘰𝘷𝘰 chromatin opening & TF binding occurs specifically post-replication, in cellular differentiation & reprogramming!

1 month ago 67 26 1 0

We wrote a perspective "How to build the regulatory genome: a constructionist guide to the cis-regulatory code", out in Development yesterday. Title says it all. Find it here:

journals.biologists.com/dev/article/...

1 month ago 39 18 1 1
Redirecting

Our most recent work on the β€œfunction and evolution” of #nuclear-speckles is now online at Cell @cp-cell.bsky.social
doi.org/10.1016/j.ce...
Read the threadπŸ‘‡ for the highlights of our findings.

1 month ago 124 60 9 5

Excited to share this work done during my PhD here in Vienna!

We show how chromatin compaction prevents the release of fragmented DNA in apoptosis, and use new tools to study the mechanism of compaction itself.

See our summary/"bluetorial" below & our preprint here: www.biorxiv.org/content/10.6...

1 month ago 28 7 2 0

New paper alert from the group!! 🚨: DNA flexibility tips the balance between stability and plasticity in nucleosomes

One of the works from my PhD, co-led alongside @nachper.bsky.social, is finally out! Work from @rcollepardo.bsky.social & @janhuemar.bsky.social
⬇️
www.biorxiv.org/content/10.6...
⬆️

2 months ago 12 6 1 2
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Excited to share @suminkim.bsky.social and @mileshuseyin.bsky.social 's new Current Opinion review on how Polycomb complexes mediate 3D genome interactions including mechanistic models and potential roles in gene regulation:
www.sciencedirect.com/science/arti...

2 months ago 60 18 1 2
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We are delighted to launch the (free!) registration for our 5th AICC symposium, hosted this year in @ucddublin.bsky.social on May 27th.

If you are interested in chromatin, gene regulation or the nucleus please join us!

allirelandchromatinconsortium.ie/annual-meeti...

2 months ago 11 8 1 3

Looking forward to it!

2 months ago 12 3 0 0
Hot Metal Bridge Post-Bac Program | The Dietrich School of Arts & Sciences Graduate Studies | University of Pittsburgh This two-semester post-baccalaureate fellowship program is designed to help talented students from groups traditionally underrepresented in their academic disciplines, including pell eligible, first g...

Know a promising undergrad who wants more time before applying to grad school? Pitt has a funded postbac program for students from underrepresented groups.

This year, my lab will consider applications for solo supervision or to be co-supervised by @mehrgol.bsky.social!

App deadline is March 15!

2 months ago 41 48 0 0
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Interested in transcriptional regulation, enhancers and 3D genome folding?

In this new study we wondered about the role of cohesin loading at enhancers for long-range transcriptional control

www.biorxiv.org/content/10.6...

detailed πŸ§΅πŸ‘‡

2 months ago 67 33 1 3
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Please join Andreas Ladurner and me for the GRC Chromatin Structure and Function conference to be held near Barcelona Spain from May 31-June 5! We accepting abstracts for posters and talks. The meeting is preceded by an awesome GRS. Learn more in our video below and apply www.grc.org/chromatin-st...

2 months ago 36 16 0 0

Want to interpret DNA sequence-to-function models to understand the underlying molecular mechanisms? Then this is a must read!

2 months ago 11 5 0 0
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DOT1L provides transcriptional memory through PRC1.1 antagonism - Nature Cell Biology Neville, Ferguson et al. show that non-canonical Polycomb repressive complex 1.1-mediated gene silencing is antagonized by DOT1L and is required for the therapeutic efficacy of Menin and DOT1L inhibit...

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

happy i could be a part of this paper from the Gilan lab out now. Along with many other things, it provides strong evidence of chromatin memory for gene activation, and suggests that DOT1L is the missing link balancing the fast and slow arms of the MLL/Polycomb axis

2 months ago 22 7 1 0

Terrific paper on a new chromosomal
compartment where extensive loop
extrusion isolates domains from
other such domains

2 months ago 36 18 0 0