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Reposted by James Davies

Radcliffe Department of Medicine @rdm.ox.ac.uk · 5d

Scientists have the most detailed view yet of how DNA folds and functions inside living cells!

The breakthrough helps us understand how genetic differences lead to disease and opens up fresh routes for drug discovery 👇

shorturl.at/nQjsx

@jojdavies.bsky.social @imm.ox.ac.uk @medsci.ox.ac.uk

Oxford scientists capture genome’s structure in unprecedented detail

RDM scientists have achieved the most detailed view yet of how DNA folds and functions inside living cells, revealing the physical structures that control when and how genes are switched on.

shorturl.at

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Reposted by James Davies

Marieke Oudelaar @mariekeoudelaar.bsky.social · 15d

Happy to share our latest publication, in which we show that the arrangement of nucleosomes around CTCF sites contributes to higher-order organisation of chromatin into TADs: www.embopress.org/doi/full/10....

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James Davies @jojdavies.bsky.social · 6d

Thanks Elzo! It has been a real pleasure collaborating with you on this.

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James Davies @jojdavies.bsky.social · 6d

Yes that’s correct - they are due to ligation junctions between the linkers of adjacent nucleosomes which have a fixed distance between them but a variable position with respect to the DNA sequence.

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Reposted by James Davies

The Lister Institute of Preventive Medicine @thelisterinstitute.bsky.social · 6d

Not from Tron or a psychedelic wallpaper. This exquisite pic reveals chromatin at base-pair resolution, captured by #ListerFellow James Davies and collaborators🤩
"For the first time, we can see how the genome's control switches are physically arranged inside cells." @jojdavies.bsky.social

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James Davies @jojdavies.bsky.social · 6d

Finally, we propose a model in which chromatin is self-organising based on histone acetylation and nucleosome depletion. We hypothesise that active cis-regulatory elements may contact one another at or above a layer of acetylated nucleosomes.

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James Davies @jojdavies.bsky.social · 6d

We then collaborated with Lothar Schermelleh to undertake super-resolution microscopy of chromatin acetylation. In keeping with his previous work we find that histone acetylation maps to regions of chromatin that are adjacent to the interchromatin compartment.

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James Davies @jojdavies.bsky.social · 6d

And histone acetylation drive the formation of the nanoscale domains we see in the MCC data.

This leads us to conclude that the biophysical properties of chromatin, particularly nucleosome depletion and histone acetylation, drive fine scale structure.

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James Davies @jojdavies.bsky.social · 6d

We show that nucleosome depletion....

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James Davies @jojdavies.bsky.social · 6d

In collaboration with Rosana Collepardo-Guevara who has develops a chemically specific molecular dynamic simulation of the physicochemical properties of chromatin, we constructed an MD simulation of the Myc promoter that closely matches the MCC data.

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James Davies @jojdavies.bsky.social · 6d

However, at other sites only the intricate structure of the nucleosome depleted region changes.

From this we conclude that nucleosome depletion itself is a major driver of long-range contacts.

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James Davies @jojdavies.bsky.social · 6d

At some sites SOX2 depletion causes complete collapse of the nucleosome depleted region at the enhancer and loss of all contacts.

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James Davies @jojdavies.bsky.social · 6d

In collaboration with Rob Klose and Elzo de Wit, we explored the role of depletion of the mediator complex components (MED14, MED13 and MED1) and transcription factors (SOX2 and NANOG).

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James Davies @jojdavies.bsky.social · 6d

We are able to map specific structures within the nucleosome depleted regions at regulatory elements that are driven by transcription factors.

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James Davies @jojdavies.bsky.social · 6d

Between nucleosome depleted regions we see nanoscale domains, that appear similar to TADs but are approximately 100- to 1000-fold smaller

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James Davies @jojdavies.bsky.social · 6d

Our latest paper has just been published in Cell!

doi.org/10.1016/j.ce...

We developed a new method called MCC ultra, which allows 3D chromatin structure to be visualised with a 1 base pair pixel size.

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Reposted by James Davies

Ben Kleinstiver @bkleinstiver.bsky.social · Sep 12

Optimization of a bespoke base editor to treat a severe pediatric vascular disease! 🫀🧬
Our manuscript describes:
1️⃣ Engineering a target-specific BE🧬
2⃣ A *must avoid* bystander edit that occurs with WT SpCas9 BEs! 🙅‍♂️
3⃣ Extension of lifespan after in vivo editing! 🐁✅

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

Treatment of a severe vascular disease using a bespoke CRISPR–Cas9 base editor in mice - Nature Biomedical Engineering

Engineering a mutant-specific customized base editor precisely corrects a mutation while minimizing bystander edits, leading to substantial phenotypic recovery in mouse models of multisystemic smooth ...

www.nature.com

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Reposted by James Davies

Davies Lab @davieslab.bsky.social · Aug 27

We’re really excited to see Hangpeng Li present our latest work at the CSH Mechanisms of Eukaryotic Transcription meeting.

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Reposted by James Davies

Nature Biotechnology @natbiotech.nature.com · Aug 26

In Brief: A new center in San Francisco will offer tailor-made CRISPR therapies to cure children with rare diseases www.nature.com/articles/s41...

Children with rare genetic diseases get CRISPR Cures center - Nature Biotechnology

Nature Biotechnology - Children with rare genetic diseases get CRISPR Cures center

www.nature.com

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Reposted by James Davies

Martin Kampmann @kampmann.bsky.social · Aug 22

Excited that the paper presenting our mouse brain in vivo CRISPR screening platform is out today in @natneuro.nature.com!

Great team effort, led by Biswa Ramani and @ivlrose.bsky.social in the Kampmann lab.

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

CRISPR screening by AAV episome-sequencing (CrAAVe-seq): a scalable cell-type-specific in vivo platform uncovers neuronal essential genes - Nature Neuroscience

The authors developed an adeno-associated virus-based high-throughput in vivo CRISPR screening platform for endogenous mouse brain cell types. Using this platform, they define genes and pathways essen...

www.nature.com

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Reposted by James Davies

Elphege Nora Lab at UCSF @elphegenoralab.bsky.social · Aug 16

New preprint with @gfudenberg.bsky.social

We find the rate of cohesin loop extrusion in cells is set by NIPBL dosage and tunes many aspects of chromosome folding.

This provides a molecular basis for NIPBL haploinsufficiency in humans. 🧵👇

www.biorxiv.org/content/10.1...

NIPBL dosage shapes genome folding by tuning the rate of cohesin loop extrusion

Cohesin loop extrusion is a major driver of chromosome folding, but how its dynamics are controlled to shape the genome remains elusive. Here we disentangle the contributions of the cohesin cofactors ...

www.biorxiv.org

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Reposted by James Davies

Beth Psaila @bethpsaila.bsky.social · Aug 15

Thrilled that our paper is in print @science.org!!
*Platelets sequester cell free DNA, including free fetal and tumour-derived DNA*
Tweetorial from @l-cmurphy.bsky.social below. Check out the news feature science.org/content/arti... and terrific editorial from Dennis Lo #platelets_in_the_limelight

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Reposted by James Davies

Nature Biotechnology @natbiotech.nature.com · Aug 6

DRAGEN rapidly identifies diverse types of genetic variants go.nature.com/4eXQRT1
rdcu.be/ezphs

Comprehensive genome analysis and variant detection at scale using DRAGEN - Nature Biotechnology

DRAGEN rapidly identifies diverse types of genetic variants.

go.nature.com

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