Rob Beagrie

Last few days to apply for this PhD project in our lab. Mix of biochemistry and structural biology, DNA replication and ubiquitin signalling. Get in touch if interested. Full application through official university portal. Deadline on 27th of November!

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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(1/n) DNA-PAINT imaging inside the nucleus at single antibody resolution using TIRF? Ultrathin sectioning makes it happen!

Grateful to share my postdoctoral work introducing “tomographic & kinetically-enhanced DNA-PAINT” or in brief: tkPAINT. Out in @pnas.org!
doi.org/10.1073/pnas...
👇🧵

New paper on the role of H3K4me3 at enhancers! We (led by Haoming Yu) used dCas9 epigenome editing to add H3K4me3 to intergenic enhancers. This was (1) sufficient to turn up transcription at open, active regions and (2) has no effect on target gene transcription. genesdev.cshlp.org/content/earl...

Most people I know are doing PE150 because it almost always ends up cheaper if you’re outsourcing. But I’d be interested to know how much fragment size affect mappability. Presumably the larger the fragment the better the chances of at least one end having a unique alignment?

Liebenberg syndrome severity arises from variations in Pitx1 locus topology and proportion of ectopically transcribing cells - Nature Communications Here the authors show that reducing enhancer-promoter distance at the Pitx1 locus increases proportion of Pitx1 forelimb expressing cells, worsening skeletal defects in Liebenberg syndrome. They also ...

Our work bridging enhancer-promoter proximity to phenotypic outcomes in vivo is out! Shout out to @olimpiabompadre.bsky.social, to Marie Kmita's lab, and to all the co-authors. www.nature.com/articles/s41...

Range extender mediates long-distance enhancer activity - Nature The REX element is associated with long-range enhancer–promoter interactions.

Our paper describing the Range Extender element which is required and sufficient for long-range enhancer activation at the Shh locus is now available at @nature.com. Congrats to @gracebower.bsky.social who led the study. Below is a brief summary of the main findings www.nature.com/articles/s41... 1/

Maternal iron deficiency causes male-to-female sex reversal in mouse embryos - Nature Iron-deficient conditions in pregnant mice can cause XY mouse embryos to develop female rather than male genitalia, revealing that iron metabolism has a role in determining male sex in mice.

This is the type of transgender mouse research that would get its money stripped away in the US... (jk jk) www.nature.com/articles/s41...

Extensive differences observed in 3D genome structure between homologous heterozygous chromosomes revealed by Genome Architecture Mapping #GAM in the @apombo1.bsky.social lab ➡️ www.embopress.org/doi/full/10....

Systematic identification of disease-causing promoter and untranslated region variants in 8040 undiagnosed individuals with rare disease #RareDisease #Genetics genomemedicine.biomedcentral.com/articles/10....

Reversible histone deacetylase activity catalyzes lysine acylation - Nature Chemical Biology Tsusaka et al. discover that histone deacetylases, which are well known to remove protein modifications, such as lysine acetylation and β-hydroxybutyrylation, can also reverse their chemical activity ...

My favorite science is the kind that makes you says, "Man, I wish I thought of that!" This is such a paper.

Mass action turns an eraser into a pen. HDACs are metabolite-dependent histone acyltransferases.

@dremilygoldberg.bsky.social @gburslem.bsky.social

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

Whole-genome sequencing analysis of anthropometric traits in 672,976 individuals reveals convergence between rare and common genetic associations Genetic association studies have mostly focussed on common variants from genotyping arrays or rare protein-coding variants from exome sequencing. Here, we used whole-genome sequence (WGS) data in 672,...

A really nice paper by @drghawkes.bsky.social et al. argues that rare and common genetic associations converge on the same genes.

While this seems at odds with our recent work about how burden tests and GWAS prioritize different genes, our results agree (🧬🧪🧵 1/6)

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

Delighted to have been able to help out with this project - congratulations Ali and the rest of the @drakesmith-lab.bsky.social - such a fascinating #genetics and #GeneRegulation story 🧪

This is going to be such a disaster. Cis-women will be outed as trans for genetics they had no idea about. What then?

Pet peeve: I hate how often ppl claim “all the researchers will just move to Europe/Canada!” You vastly under-estimate how little money there is there vs the USA- and unless that changes ASAP this loss is just going to decimate global science, full stop. 🧪🔭

I wrote up some thoughts on the idea of recruiting embattled American scientists to Europe. My main point: it would work best to keep the talent pipeline going, but not to salvage individual careers, especially mature ones. The barriers are many.

michaelerard.com/blog/a-few-t...

My son Charlie — and the breakthrough that changed our lives James Coney and his wife, Sarah, struggled not knowing why their 12-year-old was born with a severe learning disability. In their darkest moments, they blamed themselves. Then, out of the blue, came a...

A few weeks ago, I had an incredibly emotional call with James Coney, a writer for the Sunday Times whose son Charlie was in the @genomicsengland.bsky.social 100k project and was recently diagnosed with ReNU syndrome. This beautiful article tells their story ❤️ www.thetimes.com/article/0bcc...

Deletion of a single CTCF motif at the boundary of a chromatin domain with three FGF genes disrupts gene expression and embryonic development Chromatin domains delimited by CTCF can restrict the range of enhancer action. However, disruption of some domain boundaries results in mild gene dysr…

Here is the peer-reviewed version of our study showing how some TAD borders are essential for gene regulation and development.

Loss of a single CTCF motif is sufficient to cause embryonic lethality.

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

Preeclampsia risk prediction from prenatal cell-free DNA screening - Nature Medicine Using 1,854 routinely collected clinical samples from early in pregnancy, with validation in an external cohort, low-coverage cfDNA sequence data identified distinctive features among those who developed preeclampsia.

Prenatal DNA screening successfully predicts preeclampsia risk early in pregnancy, identifying tissue dysfunction months before onset.

by Adil M, Kolarova TR (...) Shree R et 15 al. in Nat Med #MedSky

📖 read the article:

The Marzi Lab in epigenetics band t-shirts

📢 Our lab is looking for a bioinformatics postdoc. We have lots of exciting projects to work on, including single cell (epi-)genomics, microglia xenotransplantations and nanopore long reads splicing analysis. Look out for the official advert next week and get in touch in the meantime 🧬🧠

Reminder of an exciting conference 'Hidden Cell, Dark Genome', Edinburgh 3-4th April 2025!

Sessions:
• Regulatory functions of the dark genome
• Uncharted proteins and RNA complexity
• Cellular diversity
• Atomic structures at the cellular scale

Early bird and registration deadline: 28th February!

SCIENCESHOTS What does a scientist look like? Children are drawing women more than ever before

When asked to draw a scientist, school-age kids in the United States are increasingly sketching women, according to a study from 2018.

Read more on #WomenInScienceDay: https://scim.ag/4hOUuvx

Nothing in life is to be feared, it is only to be understood. Marie Curie, Physicist and chemist.

Today is International Day of Women & Girls in Science.

Marie Curie, the first woman to win a Nobel Prize. Her contributions have left an indelible mark on the world of science & health & continue to inspire generations of scientists & innovators. 🔬 #WomenInScience #WomenInSTEM

Anyone else worried about what might happen if funding gets pulled for the Gene Expression Omnibus? Is everything mirrored at EBI or only some of it? #genomics #bioinformatics

Prenatal stress effects on the placenta.

Maternal stress is a critical factor in the long-term health of offspring. A recent study (below) profiled the effects of prenatal stress on DNA methylation + gene expression in rat placenta & fetal brain.
🧪🧠🐀 #neuroskyence
www.nature.com/articles/s41...

Job alert!

We are hiring a postdoc or PhD student focusing on
* developing computational methods to resolve gene regulation in single cells
* investigating the mechanisms and cell-type specific effects of genetic variants

PhD student: bsky.app/profile/jobr...

Postdoc: bsky.app/profile/jobr...

Disruption of chromatin contacts by cohesin being at least as important as stabilisation has been one of my pet hypotheses for a while now - nice to see this properly reasoned out in print!

Multiplexed spatial mapping of chromatin features, transcriptome and proteins in tissues - Nature Methods Spatial-Mux-seq offers a multimodal spatial platform capable of profiling multiple molecular modalities, including the transcriptome, chromatin accessibility, histone modifications and targeted protei...

Multiplexed spatial mapping of chromatin features, transcriptome and proteins in tissues www.nature.com/articles/s41...

KMT2C/KMT2D-dependent H3K4me1 mediates changes in DNA replication timing and origin activity during a cell fate transition Gökbuget et al. use machine learning to quantify chromatin state changes that predict DNA replication timing changes during cell differentiation. By following up on top predictors through functional v...

🚨 New Paper Alert! 🚨
Our latest study on KMT2C/KMT2D (mutated in 20% of cancers) reveals a new function for H3K4me1 in regulating DNA replication timing (RT) and origin activity during cell state transitions. Check it out: www.cell.com/cell-reports.... More info ⬇️