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Stefan Schoenfelder

@stefanschoenfelder.bsky.social

Enhancers, 3D genome organisation, pluripotent stem cells Babraham Institute and Enhanc3D Genomics

742 Followers  |  528 Following  |  126 Posts  |  Joined: 25.01.2025
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Posts by Stefan Schoenfelder (@stefanschoenfelder.bsky.social)

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Pls re-post: My department @oxfordbiochemistry.bsky.social are recruiting for several new faculty positions (links below). Broad search in molecular biology/biochemistry, across prokaryotes and eukaryotes. Interested in understanding life at the molecular level, this job might be for you!
1/n

05.03.2026 21:35 β€” πŸ‘ 87    πŸ” 125    πŸ’¬ 2    πŸ“Œ 3

Excellent opportunities in a top lab!

06.03.2026 11:30 β€” πŸ‘ 1    πŸ” 0    πŸ’¬ 0    πŸ“Œ 0
Figure 1.(A) Classical gel electrophoresis experiments showing mono-, di-, tri-, tetra-, and further multinucleosome bands upon chromatin digestion. (B) The nucleosome repeat length (NRL) is defined as the genomic distance between the centres of two neighbouring nucleosomes.

Figure 1.(A) Classical gel electrophoresis experiments showing mono-, di-, tri-, tetra-, and further multinucleosome bands upon chromatin digestion. (B) The nucleosome repeat length (NRL) is defined as the genomic distance between the centres of two neighbouring nucleosomes.

Figure 2.Nucleosome mapping using MNase-seq versus ATAC-seq. (A) In MNase-seq, nucleosomes in both open and tightly packed genomic regions are accessible to digestion. MNase preferentially cleaves DNA between nucleosomes and digests DNA until it encounters a histone octamer, which provides a footprint of nucleosome-protected DNA regions. (B) Bulk MNase-seq results in averaged maps across millions of cells, effectively capturing all possible nucleosome positioning configurations. (C) Single-cell MNase-seq (scMNase-seq) results in a noisier and sparser signal. The resulting footprints still represent nucleosome-protected regions, but not all nucleosomes are represented. (D) In ATAC-seq, open regions can be accessed by the enzyme Tn5 transposase, which can insert primers in regions free from the binding of nucleosomes and transcription factors (TFs). (E) For open chromatin regions, nucleosome maps can be obtained from ATAC-seq similar to MNase-seq. (F) Closed, tightly packed chromatin regions may be less represented in ATAC-seq nucleosome maps.

Figure 2.Nucleosome mapping using MNase-seq versus ATAC-seq. (A) In MNase-seq, nucleosomes in both open and tightly packed genomic regions are accessible to digestion. MNase preferentially cleaves DNA between nucleosomes and digests DNA until it encounters a histone octamer, which provides a footprint of nucleosome-protected DNA regions. (B) Bulk MNase-seq results in averaged maps across millions of cells, effectively capturing all possible nucleosome positioning configurations. (C) Single-cell MNase-seq (scMNase-seq) results in a noisier and sparser signal. The resulting footprints still represent nucleosome-protected regions, but not all nucleosomes are represented. (D) In ATAC-seq, open regions can be accessed by the enzyme Tn5 transposase, which can insert primers in regions free from the binding of nucleosomes and transcription factors (TFs). (E) For open chromatin regions, nucleosome maps can be obtained from ATAC-seq similar to MNase-seq. (F) Closed, tightly packed chromatin regions may be less represented in ATAC-seq nucleosome maps.

Figure 5.Molecular mechanisms affecting nucleosome spacing. (A) Linker histones H1 and nonhistone chromatin proteins which compete with H1s and modulate nucleosome spacing through structural and electrostatic mechanisms. (B) Chromatin remodellers actively reposition nucleosomes following context-dependent rules. (C) Cell state-dependent chromatin boundaries formed by CTCF and other structural proteins, as well as associated recruitment of chromatin remodellers which space nucleosomes. (D) Gene activity associated with remodeller action and RNA polymerases transcribing through the nucleosomes, leading to smaller distances between nucleosomes in regulatory regions and gene bodies. (E) DNA sequence repeats of different types.

Figure 5.Molecular mechanisms affecting nucleosome spacing. (A) Linker histones H1 and nonhistone chromatin proteins which compete with H1s and modulate nucleosome spacing through structural and electrostatic mechanisms. (B) Chromatin remodellers actively reposition nucleosomes following context-dependent rules. (C) Cell state-dependent chromatin boundaries formed by CTCF and other structural proteins, as well as associated recruitment of chromatin remodellers which space nucleosomes. (D) Gene activity associated with remodeller action and RNA polymerases transcribing through the nucleosomes, leading to smaller distances between nucleosomes in regulatory regions and gene bodies. (E) DNA sequence repeats of different types.

Figure 6. Examples of NRL changes in biological systems. (A) Cell differentiation leads to NRL changes between different cell types, e.g. mouse dorsal root ganglia neurons (NRL ∼165 bp) versus cortical astrocytes (NRL ∼183 bp) [175]. Schematic cell shapes are adapted from an image created in BioRender (https://BioRender.com/89trj2t). (B) Paired normal versus tumour breast tissues show NRL shortening in cancer (figure adapted from [36] under the CC BY 4.0 licence (https://creativecommons.org/licenses/by/4.0/)). (C) Nucleosome positioning derived from cfDNA of human volunteers shows NRL increase with age (figure reprinted from [79] under the CC BY 4.0 licence (https://creativecommons.org/licenses/by/4.0/)).

Figure 6. Examples of NRL changes in biological systems. (A) Cell differentiation leads to NRL changes between different cell types, e.g. mouse dorsal root ganglia neurons (NRL ∼165 bp) versus cortical astrocytes (NRL ∼183 bp) [175]. Schematic cell shapes are adapted from an image created in BioRender (https://BioRender.com/89trj2t). (B) Paired normal versus tumour breast tissues show NRL shortening in cancer (figure adapted from [36] under the CC BY 4.0 licence (https://creativecommons.org/licenses/by/4.0/)). (C) Nucleosome positioning derived from cfDNA of human volunteers shows NRL increase with age (figure reprinted from [79] under the CC BY 4.0 licence (https://creativecommons.org/licenses/by/4.0/)).

Nucleosome aficionados! Our new review "Nucleosome spacing across cell types, diseases, and ages" is out in NAR: academic.oup.com/nar/article/...

A huge effort to pull together what we’ve learned about nucleosome spacing in many systems. Enjoy!
@milena-bikova.bsky.social @chrsclrksn.bsky.social

05.03.2026 21:33 β€” πŸ‘ 46    πŸ” 18    πŸ’¬ 0    πŸ“Œ 1

Several COVID-19 severity associated genetic variants demonstrably change enhancer activity. Check out @gweykopf.bsky.social's preprint using STARR-seq and deep learning models to identify and get insight into some of these variants.

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

05.03.2026 08:42 β€” πŸ‘ 9    πŸ” 1    πŸ’¬ 1    πŸ“Œ 0
LinkedIn This link will take you to a page that’s not on LinkedIn

I am very excited to host @danielibrahim.bsky.social for this talk β€œEnhancer-promoter specificity is determined by the promoter-proximal region” in our @enhancedgenomics.bsky.social seminar series β€˜The 3D Regulatory Genome’

πŸ“… 05 March 2026 (today!)
⏰ 4 pm GMT

Please join us:
lnkd.in/eJ86KFNg

05.03.2026 13:14 β€” πŸ‘ 3    πŸ” 0    πŸ’¬ 0    πŸ“Œ 1
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Systematic investigation of interindividual variation of DNA methylation in human whole blood - Genome Biology Background Interindividual genetic variability is well characterised, but we still lack a complete catalogue of loci displaying variable and stable epigenetic patterns. Results Here, we report a catal...

Excited to share our latest publication on interindividual variation of DNA methylation in human whole blood, spearheaded by the amazing Olivia Grant and co-led with @leo-schalkwyk.bsky.social and Meena Kumari.

link.springer.com/article/10.1...

05.03.2026 10:56 β€” πŸ‘ 19    πŸ” 10    πŸ’¬ 2    πŸ“Œ 0

Proud of @juruehle.bsky.social for getting her PhD paper on biorxiv! In it, we take synthetic enhancer screens to the single cell level, offering new insight into how transcription factors and enhancers interact πŸ‘€

04.03.2026 11:31 β€” πŸ‘ 15    πŸ” 4    πŸ’¬ 0    πŸ“Œ 0
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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...

04.03.2026 23:58 β€” πŸ‘ 55    πŸ” 23    πŸ’¬ 1    πŸ“Œ 2

If you want to explore ncRNA dynamics during mammalian development, love microscopy, and are not afaraid of transposons biology, apply‼️
We are looking for a postdoc to join our team at @imbavienna.bsky.social
More details πŸ‘‡πŸ»

02.03.2026 12:25 β€” πŸ‘ 23    πŸ” 28    πŸ’¬ 0    πŸ“Œ 0
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The role of KRAB zinc-finger proteins in expanding the domestication potential of transposable elements - Nature Genetics This Perspective explores the co-evolution of transposable elements and KRAB zinc-finger proteins in relation to their integration into human gene regulatory networks, highlighting their potential eff...

Find our latest Perspective article in Nature Genetics on "The role of KRAB zinc-finger proteins in expanding the domestication potential of transposable elements" at www.nature.com/articles/s41..., with implications for the future of research on the cause of human disease.

02.03.2026 13:40 β€” πŸ‘ 38    πŸ” 18    πŸ’¬ 0    πŸ“Œ 1
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Photorespiration is linked to DNA methylation by formate as a one-carbon source - Nature Plants This study reveals that Arabidopsis reassimilates formate produced during photorespiration via the cytosolic folate cycle to fuel DNA methylation, forming a metabolic–epigenetic bridge that links elev...

Delighted to share our paper, out today in @natplants.nature.com

Not all β€œwasted” carbon is lost: formate released during photorespiration can be reused to support DNA methylation. Our work reveals a metabolic link between COβ‚‚ levels and epigenetic regulation in Arabidopsis.
doi.org/10.1038/s414...

25.02.2026 11:38 β€” πŸ‘ 26    πŸ” 7    πŸ’¬ 2    πŸ“Œ 3

I’m thrilled to share that my PhD work has been just published in Cell. After a long and bumpy ride, we uncovered the core function of nuclear speckles -splicing of GC-levelled exons- and traced the evolution of this gene architecture and condensates themselves to amniotes.

25.02.2026 16:53 β€” πŸ‘ 70    πŸ” 18    πŸ’¬ 0    πŸ“Œ 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/...

27.02.2026 19:51 β€” πŸ‘ 33    πŸ” 15    πŸ’¬ 0    πŸ“Œ 0
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Chromatin spatial analysis by METALoci unveils sex-determining 3D regulatory hubs Nature Structural & Molecular Biology - METALoci, a new three-dimensional genome computational tool, reveals a major rewiring of regulatory interactions during sex determination. By combining...

🀩πŸ’ͺ Out now! 3D regulatory hubs in sex determination

With @mamartirenom.bsky.social & Capel labs, led by @imotagom.bsky.social & @jrotwitguez.bsky.social

1️⃣ METALoci – explore #3DGenome 🧬
2️⃣ Non-coding region controlling Fgf9 🧩
3️⃣ Meis genes = new key players 🌟

πŸ‘‰ rdcu.be/e5sm2

1/n Bluetorial πŸ‘‡

24.02.2026 14:02 β€” πŸ‘ 59    πŸ” 26    πŸ’¬ 1    πŸ“Œ 2

We wrote a piece on how easy it is to write gene regulatory sequences. - Turns out, it isn't that easy even though we know a lot about cis-regulation.

huge credit to @carldeboer.bsky.social to seeing this through so our thoughts aren't lost. I promise, it's a worthwhile read!

27.02.2026 08:27 β€” πŸ‘ 28    πŸ” 12    πŸ’¬ 0    πŸ“Œ 0

Incredibly proud to share our new preprint, lead by the Incomparable Rithika Sankar.
Here we temporally dissect the role of FACT in mES cells, finding that FACT loss drives progressive deterioration of chromatin architecture, leading to transcriptional collapse.
www.biorxiv.org/content/10.6...

27.02.2026 21:27 β€” πŸ‘ 43    πŸ” 26    πŸ’¬ 1    πŸ“Œ 1
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🧬 @danielibrahim.bsky.social, moderated by @stefanschoenfelder.bsky.social, on enhancer-promoter specificity & how promoter-proximal regions act as molecular filters.

Register: us02web.zoom.us/webinar/regi...

March 5, 4PM UK.

#Genomics #GeneRegulation

26.02.2026 13:37 β€” πŸ‘ 18    πŸ” 6    πŸ’¬ 0    πŸ“Œ 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.

25.02.2026 16:01 β€” πŸ‘ 122    πŸ” 59    πŸ’¬ 9    πŸ“Œ 5

Join us tomorrow for two exciting enhancer talks!

24.02.2026 19:45 β€” πŸ‘ 6    πŸ” 4    πŸ’¬ 0    πŸ“Œ 0
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Save the date!
We have an exciting conference coming up next year for the UK Mechanobiology community!

23.02.2026 18:13 β€” πŸ‘ 17    πŸ” 8    πŸ’¬ 0    πŸ“Œ 1

Our work on the interplay between loop extrusion and chromatin mechanics is finally out in @physrevresearch.bsky.social . Congrats @hosseinsalari.bsky.social for the hard work ! πŸ‘
journals.aps.org/prresearch/a...

23.02.2026 13:00 β€” πŸ‘ 16    πŸ” 8    πŸ’¬ 0    πŸ“Œ 0

Sorry to clarify: the relatively low success rate (compared to our RNA-seq and ATAC-seq libraries) is something we see across antibodies; it’s not H3K27ac specific. They eventually all work - we just have to repeat more than I’d like.

23.02.2026 14:54 β€” πŸ‘ 1    πŸ” 0    πŸ’¬ 0    πŸ“Œ 0

Thanks Matthias. Our H3K27ac CUT&Tag libraries are definitely usable but we’ve found the FRiP scores are consistently lower than for ChIP-seq. We’ve tried several different antibodies. Might just be us though of course

23.02.2026 14:51 β€” πŸ‘ 1    πŸ” 0    πŸ’¬ 0    πŸ“Œ 0

Would love to hear if others have had similar experiences - many thanks for sharing in advance

22.02.2026 22:38 β€” πŸ‘ 1    πŸ” 0    πŸ’¬ 0    πŸ“Œ 0

2.) Even more frustratingly, our 'hit ratio' for CUT&Tag is still quite low. I would estimate 90-95% of our RNA-seq and ATAC-seq libraries are high quality, but for CUT&Tag it's closer to 60%. It's not a batch effect, it's not antibody-specific - frustratingly we've never been able to figure out why

22.02.2026 22:37 β€” πŸ‘ 1    πŸ” 0    πŸ’¬ 1    πŸ“Œ 1

1.) some histone mods antibodies work beautifully (H3K4me3, H3K27me3) but others produce noisier profiles. For example, for H3K27ac in our hands ChIP-seq is still superior (which is a pain!).

22.02.2026 22:33 β€” πŸ‘ 1    πŸ” 0    πŸ’¬ 2    πŸ“Œ 0

We use CUT&Tag a lot (haven't tried CUT&Run yet) and in general I'm a big fan. The two major issues we've encountered are (this is mainly for human iPSCs):

22.02.2026 22:32 β€” πŸ‘ 1    πŸ” 0    πŸ’¬ 1    πŸ“Œ 0

Hey Chromatin Friends!
Long time no chromatin question...
For many of you, CUT&x (RUN/Tag) works really well but some of you have had their frustrations with CUT and "gone back" to ChIP-Seq. Can you share your experiences in the comments!?
Would love to hear from you!
Sharing is appreciated : )

19.02.2026 16:26 β€” πŸ‘ 14    πŸ” 10    πŸ’¬ 2    πŸ“Œ 0

And a new paper from the lab. A follow up to a previous study in which we elucidate the mechanism of the nuclear transport. Read the full story: www.nature.com/articles/s41...

11.02.2026 17:12 β€” πŸ‘ 41    πŸ” 21    πŸ’¬ 1    πŸ“Œ 0
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The $100 whole human genome sequence finally reached!
www.sandiegouniontribune.com/2026/02/19/s...

20.02.2026 20:29 β€” πŸ‘ 258    πŸ” 77    πŸ’¬ 12    πŸ“Œ 11