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Linxuan Zhao

@linxuanzhao

PhD student @Bienko Lab @Karolinska Institute and @SciLifeLab | 3D genome organization | Single-cell genomics | Method development

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Latest posts by Linxuan Zhao @linxuanzhao

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Nuclear speckles enable processing of RNA from GC-rich isochores Nuclear speckles are key subnuclear structures that regulate gene expression in GC-rich regions. This work shows that the evolution and expansion of core speckle proteins were crucial for the increase...

The function of nuclear speckles is revealed! This is an incredibly important paper with absolutely beautiful data! Wow! www.cell.com/cell/fulltex...

25.02.2026 17:43 πŸ‘ 39 πŸ” 15 πŸ’¬ 1 πŸ“Œ 1
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Please check out our new review on emerging oligo-based imaging methods in studying chromatin organization, which summarizes recent advances in DNA FISH and its applications in chromatin tracing, live-cell imaging, lineage reconstruction, and optical pooled screening.

Link: bit.ly/46YV3Qb

22.02.2026 23:32 πŸ‘ 5 πŸ” 0 πŸ’¬ 0 πŸ“Œ 0
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Mechanistic and Epigenetic Partitioning of Lamina-Associated Chromatin Revealed by a Genome-Wide Imaging Screen The nuclear periphery is a key site for heterochromatin organization in eukaryotic cells, where lamina-associated domains (LADs) promote transcriptional repression and genome stability. Despite their ...

🚨New preprint from the lab🚨
🧬 What keeps certain chromatin domains anchored at the nuclear periphery? Our new genome-wide HiDRO screen uncovers a key role for RNA-binding protein hnRNPK.
www.biorxiv.org/content/10.1...

14.08.2025 19:01 πŸ‘ 61 πŸ” 24 πŸ’¬ 0 πŸ“Œ 2
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Ab-trapping - a peripheral staining artifact in antibody-based microscopy and genomics Antibodies (Ab) are essential for detecting specific epitopes in microscopy and genomics, but can produce artifacts leading to erroneous interpretations. Here, we characterize a novel artifact, Ab-tra...

🚨 Preprint alert 🚨
Excited to share our work on "Ab-trapping," an antibody artifact causing misleading peripheral ("rim") staining in imaging & genomics (IF, CUT&Tag, CUT&RUN). Antibodies fail to penetrate structures, accumulating at the periphery. A πŸ§΅πŸ‘‡
doi.org/10.1101/2025...

14.04.2025 20:08 πŸ‘ 69 πŸ” 41 πŸ’¬ 2 πŸ“Œ 9

Our new findings on how chromosomes get ready for cell division are now published in @cellpress.bsky.social!

Congratulations, Kai, @andibrunner.bsky.social and everyone else involved! 🀩

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

24.03.2025 15:29 πŸ‘ 73 πŸ” 40 πŸ’¬ 1 πŸ“Œ 1
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Brown University Professor and Doctor Are Deported to Lebanon Despite a Judge’s Order Dr. Rasha Alawieh, a kidney transplant specialist and Brown University professor who had a valid visa, was expelled in apparent defiance of a court order.

Brown University Professor and kidney transplant expert is deported despite valid visa, judge's order, and petition.

www.nytimes.com/2025/03/16/u...

16.03.2025 20:59 πŸ‘ 18 πŸ” 12 πŸ’¬ 0 πŸ“Œ 0
Graphical abstract for Binan et al., Simultaneous CRISPR screening and spatial transcriptomics reveal intracellular, intercellular, and functional transcriptional circuits

Graphical abstract for Binan et al., Simultaneous CRISPR screening and spatial transcriptomics reveal intracellular, intercellular, and functional transcriptional circuits

Fantastic work from my soon-to-be neighbour Loϊc Binan (and all)! Simultaneous CRISPR screening and spatial transcriptomics reveal intracellular, intercellular, and functional transcriptional circuits
www.cell.com/cell/fulltex...

12.03.2025 21:18 πŸ‘ 9 πŸ” 4 πŸ’¬ 0 πŸ“Œ 0
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UMASS IS RESCINDING ALL GRAD POSITIONS FOR THIS YEAR

12.03.2025 19:00 πŸ‘ 2580 πŸ” 1275 πŸ’¬ 146 πŸ“Œ 409

Sequencing by Expansion (SBX) -- a novel, high-throughput single-molecule sequencing technology https://www.biorxiv.org/content/10.1101/2025.02.19.639056v1

24.02.2025 21:33 πŸ‘ 36 πŸ” 19 πŸ’¬ 0 πŸ“Œ 4
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Pervasive and programmed nucleosome distortion patterns on single mammalian chromatin fibers We present a genome-scale method to map the single-molecule co-occupancy of structurally distinct nucleosomes, subnucleosomes, and other protein-DNA interactions via long-read high-resolution adenine ...

Amid concerning times, sharing a bit of positivity: our 1st preprint of 2025 (funded VIA NIH COMMON FUND), heroically led by Marty Yang (@martyyang.bsky.social) w/ huge assist from @genophoria.bsky.social lab. Lots to cover so let’s get this tweetorial started (1/n)! www.biorxiv.org/content/10.1...

24.01.2025 01:04 πŸ‘ 70 πŸ” 22 πŸ’¬ 4 πŸ“Œ 3
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Thermodynamic principles link in vitro transcription factor affinities to single-molecule chromatin states in cells The molecular details governing transcription factor (TF) binding and the formation of accessible chromatin are not yet quantitatively understood - including how sequence context modulates affinity, h...

Thermodynamic principles link in vitro transcription factor affinities to singlemolecule chromatin states in cells

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

30.01.2025 17:12 πŸ‘ 29 πŸ” 12 πŸ’¬ 0 πŸ“Œ 0
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A temperature-inducible protein module for control of mammalian cell fate - Nature Methods The Melt (Membrane localization using temperature) protein translocates to the plasma membrane upon temperature shift. Melt variants with a range of switching temperatures enable straightforward therm...

Every once in a while we publish a paper that moves a whole field forward. I think that's the case for this one from the Bugaj lab, where they describe proteins for THERMOGENETIC control of cellular behavior. www.nature.com/articles/s41...

23.01.2025 18:34 πŸ‘ 1211 πŸ” 149 πŸ’¬ 37 πŸ“Œ 13

It’s official πŸŽ‰ I am excited to share that I will start my lab this spring at the Max Planck Institute for Immunobiology and Epigenetics @mpi-ie.bsky.social in beautiful Freiburg πŸ€©πŸ—»β˜€οΈ I am looking forward to new collaborations and working with the fantastic community in Freiburg & its surroundings!

16.01.2025 18:38 πŸ‘ 181 πŸ” 31 πŸ’¬ 28 πŸ“Œ 5
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Excited to share James Jusuf's preprint:

By integrating Micro-C with SuperRes Live-Imaging we can calibrate genomics&imaging to perform absolute quantification of looping (e.g. this loop is present 3%)

We quantify mESC 36k loops: <loops> are generally rare (2.3%)

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

16.01.2025 13:35 πŸ‘ 151 πŸ” 64 πŸ’¬ 6 πŸ“Œ 2
Enhancer scrambling strategy

Enhancer scrambling strategy

We are happy to share our enhancer scramble story, a strategy to create hundreds of stochastic deletions, inversions, and duplications within mammalian gene regulatory regions and associate these new architectures with gene expression levels 🧡
www.biorxiv.org/content/10.1...

15.01.2025 20:32 πŸ‘ 183 πŸ” 77 πŸ’¬ 3 πŸ“Œ 2
Single cell – ENCODEHomo sapiens clickable body map

Very excited to announce that the single cell/nuc. RNA/ATAC/multi-ome resource from ENCODE4 is now officially public. This includes raw data, processed data, annotations and pseudobulk products. Covers many human & mouse tissues. 1/

www.encodeproject.org/single-cell/...

07.01.2025 21:29 πŸ‘ 287 πŸ” 86 πŸ’¬ 6 πŸ“Œ 0
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How to test the functional impact of non-coding variants in vivo? We developed a new method called dual-enSERT, which can quantitatively compare the effects of enhancer variants in live mouse embryos in under two weeks. www.nature.com/articles/s41... 1/n

06.01.2025 14:55 πŸ‘ 87 πŸ” 33 πŸ’¬ 4 πŸ“Œ 1
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Single-cell mapping of regulatory DNA:Protein interactions Gene expression is coordinated by a multitude of transcription factors (TFs), whose binding to the genome is directed through multiple interconnected epigenetic signals, including chromatin accessibil...

🧬 We’re excited to introduce D&D-seq, a single-cell technology that maps DNA:Protein interactions through molecular footprinting. Check it out here: biorxiv.org/content/10.1... #Genomics #Epigenetics

02.01.2025 21:10 πŸ‘ 54 πŸ” 14 πŸ’¬ 3 πŸ“Œ 1

Is chromatin ordered or disordered? It all depends on the linker DNA length.

Check our latest work with Mike Rosen and Sy Redding. We explore how changes in linker DNA length (as small as 1 bp) fine-tune chromatin structure, between order and disorder, and the properties of chromatin droplets

24.12.2024 09:48 πŸ‘ 114 πŸ” 38 πŸ’¬ 6 πŸ“Œ 3
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Deaminase-mediated chromatin accessibility profiling with single-allele resolution www.biorxiv.org/content/10.1...

23.12.2024 18:50 πŸ‘ 9 πŸ” 2 πŸ’¬ 0 πŸ“Œ 0
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We often speak about chromatin as being accessible or inaccessible, but what does it mean? We wrote a short review on this, πŸ”¬ focused:

sciencedirect.com/science/arti...

A big thank you to Tom Fillot for his efforts on this and to
@hansen_lab

@marcelonollmann
for their help as editors.

20.12.2024 15:46 πŸ‘ 136 πŸ” 55 πŸ’¬ 4 πŸ“Œ 3
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1/πŸš€ Excited to share RegVelo, our new cell model combining RNA velocity with gene regulatory network (GRN) dynamics to model cellular changes and predict in silico perturbations. Here's how it works and why it matters! πŸ§΅πŸ‘‡
biorxiv.org/content/10.1101/2024.12.11.627935v1

12.12.2024 14:48 πŸ‘ 112 πŸ” 47 πŸ’¬ 3 πŸ“Œ 4
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Evolution and function of chromatin domains across the tree of life - Nature Structural & Molecular Biology Szalay et al. discuss cross-kingdom similarities and differences in 3D chromatin folding in relation to gene regulation, including in bacteria, archaea, mammals and plants. This comparison reveals cer...

πŸ”ΊπŸ”ΊπŸ”ΊRED TRIANGLE ALERT πŸ”ΊπŸ”ΊπŸ”Ί
Ever wonder how #TADs compare across the tree of life?Look no further & read our Review!!!

Find out what genes & 3D chromatin can & can't do in Bacteria! Archeae! Yeast! Plants! Animals!

SMCs & RNA-Pol are the only thing they have in common
www.nature.com/articles/s41...

28.11.2024 12:48 πŸ‘ 206 πŸ” 84 πŸ’¬ 3 πŸ“Œ 5
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ChIP-DIP maps binding of hundreds of proteins to DNA simultaneously and identifies diverse gene regulatory elements - Nature Genetics ChIP-DIP (ChIP done in parallel) is a highly multiplex assay for protein–DNA binding, scalable to hundreds of proteins including modified histones, chromatin regulators and transcription factors, offe...

Gene regulation involves thousands of proteins that bind DNA, yet comprehensively mapping these is challenging. Our paper in Nature Genetics describes ChIP-DIP, a method for genome-wide mapping of hundreds of DNA-protein interactions in a single experiment.
www.nature.com/articles/s41...

27.11.2024 04:13 πŸ‘ 383 πŸ” 150 πŸ’¬ 9 πŸ“Œ 22
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Science Magazine on LinkedIn: This light-sheet microscopy three-dimensional rendering shows a… This light-sheet microscopy three-dimensional rendering shows a first-of-its-kind mouse whole-brain mRNA analysis at single-cell resolution. Learn more in…

Thrilled to announce that our latest work has been published in Science and featured on the front cover!

www.linkedin.com/posts/scienc...

22.11.2024 00:43 πŸ‘ 53 πŸ” 12 πŸ’¬ 4 πŸ“Œ 3
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It's my great pleasure to present the next big preprint from SheqLab! An exciting application of our O-MAP platform that I hope will transform the study of nuclear architecture.
If you've ever wanted to dissect the subnuclear "neighborhood" around an individual locus, read on! (1/30)

21.11.2024 01:27 πŸ‘ 185 πŸ” 76 πŸ’¬ 11 πŸ“Œ 9
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Transcription of a centromere-enriched retroelement and local retention of its RNA are significant features of the CENP-A chromatin landscape - Genome Biology Background Centromeres depend on chromatin containing the conserved histone H3 variant CENP-A for function and inheritance, while the role of centromeric DNA repeats remains unclear. Retroelements are...

Our paper on a centromere-enriched retroelement is out! link.springer.com/article/10.1... Congratulations to all the authors! Comments and reposts welcome and appreciated πŸ§¬πŸ”¬

18.11.2024 17:50 πŸ‘ 80 πŸ” 45 πŸ’¬ 4 πŸ“Œ 1
PCP maps 3D genome organization at the nucleosome level.
(a) Schematic of the PCP reaction on chromatin. Crosslinked chromatin is digested into nucleosomes by Caspase Activated DNAse (CAD) and then immobilized onto magnetic beads. Digested chromatin is ligated by seed and receptor molecules to the ratio of 1/10. The PCP reaction takes place on the beads where RNA tags will diffuse from the seeds and tag nearby receptors. The chromatin is then decrosslinked, the proteins and RNA removed, and a sequencing library generated by PCR. Molecules sharing the same UMI are grouped. Tag groups can be analyzed in several ways, including individual multiway tag groups or pairwise interaction matrices. (b) Plot showing the relative frequency of receptor tagging as a function of distance from the seed, the midpoints of the tagged molecules is shown. Seeds that self-tag are excluded from this analysis. (c) Plot showing the number of reads per seed tag groups for G1 data. (d) Distance decay interaction plots of PCP (orange) and Micro-C (Costantinto et al. 2020, 15 min 23Β°C sample) (res = 50bp).

PCP maps 3D genome organization at the nucleosome level. (a) Schematic of the PCP reaction on chromatin. Crosslinked chromatin is digested into nucleosomes by Caspase Activated DNAse (CAD) and then immobilized onto magnetic beads. Digested chromatin is ligated by seed and receptor molecules to the ratio of 1/10. The PCP reaction takes place on the beads where RNA tags will diffuse from the seeds and tag nearby receptors. The chromatin is then decrosslinked, the proteins and RNA removed, and a sequencing library generated by PCR. Molecules sharing the same UMI are grouped. Tag groups can be analyzed in several ways, including individual multiway tag groups or pairwise interaction matrices. (b) Plot showing the relative frequency of receptor tagging as a function of distance from the seed, the midpoints of the tagged molecules is shown. Seeds that self-tag are excluded from this analysis. (c) Plot showing the number of reads per seed tag groups for G1 data. (d) Distance decay interaction plots of PCP (orange) and Micro-C (Costantinto et al. 2020, 15 min 23Β°C sample) (res = 50bp).

Regularly spaced nucleosome arrays are prevalent over the genome.
(a) Meta analysis of PCP matrices relative to the dyad of the +1 nucleosome of genes longer than 2Kb, 50 least expressed genes (res = 10bp). (b) As a, but for the 50 most expressed genes (res = 10bp). (c) PCP map of low expressed gene RNR3 (middle, res = 25bp), Nucleosome profile (grey). Note the grid-like pattern across the entire gene body. (d) PCP map of the expressed gene FMP27 (res = 25bp), Nucleosome profile (grey). Note the grid-like pattern at the 5’ end of the gene and parallel stripes at towards the middle and 3’ end of gene. (e) Schematic of the results observed. No pattern is obtained with poorly spaced, poorly positioned nucleosomes. Dotted pattern is obtained with regularly spaced, well positioned nucleosome arrays. Striped pattern is obtained with regularly spaced delocalized arrays. The number of parallel stripes indicates the number of nucleosomes in the array. (f) Meta plot of highly transcribed, ribosomal protein genes. The genes are organized with respect to the Rap1 protein at position 0. Top panel, Rap1 ChIP-MNase in blue (Gutin et al. 2018), All reads size, Mono-nucleosomal (Nuc.) reads only and Sub-nucleosomal reads only (Sub. 20 bp < insert size < 90 bp) are represented. Medium panel represent the density of read by position relative to insert size from mapped PCP data. The bottom panel is a pile-up analysis of PCP matrix oriented relative to the RP genes (res = 10bp). Note that the gene body contains short, delocalized nucleosome arrays. (g) Frequency of tagging relative to the seed position for the subset of genes used in a and b. The most expressed genes are in red and least expressed genes in blue. (h) Frequency of tagging relative to the seed position for gene of at least 600bp. The most expressed are in orange and the least expressed is in blue.

Regularly spaced nucleosome arrays are prevalent over the genome. (a) Meta analysis of PCP matrices relative to the dyad of the +1 nucleosome of genes longer than 2Kb, 50 least expressed genes (res = 10bp). (b) As a, but for the 50 most expressed genes (res = 10bp). (c) PCP map of low expressed gene RNR3 (middle, res = 25bp), Nucleosome profile (grey). Note the grid-like pattern across the entire gene body. (d) PCP map of the expressed gene FMP27 (res = 25bp), Nucleosome profile (grey). Note the grid-like pattern at the 5’ end of the gene and parallel stripes at towards the middle and 3’ end of gene. (e) Schematic of the results observed. No pattern is obtained with poorly spaced, poorly positioned nucleosomes. Dotted pattern is obtained with regularly spaced, well positioned nucleosome arrays. Striped pattern is obtained with regularly spaced delocalized arrays. The number of parallel stripes indicates the number of nucleosomes in the array. (f) Meta plot of highly transcribed, ribosomal protein genes. The genes are organized with respect to the Rap1 protein at position 0. Top panel, Rap1 ChIP-MNase in blue (Gutin et al. 2018), All reads size, Mono-nucleosomal (Nuc.) reads only and Sub-nucleosomal reads only (Sub. 20 bp < insert size < 90 bp) are represented. Medium panel represent the density of read by position relative to insert size from mapped PCP data. The bottom panel is a pile-up analysis of PCP matrix oriented relative to the RP genes (res = 10bp). Note that the gene body contains short, delocalized nucleosome arrays. (g) Frequency of tagging relative to the seed position for the subset of genes used in a and b. The most expressed genes are in red and least expressed genes in blue. (h) Frequency of tagging relative to the seed position for gene of at least 600bp. The most expressed are in orange and the least expressed is in blue.

Interesting new method to map nucleosomes in 3D, "Proximity Copy Paste (PCP)". www.biorxiv.org/content/10.1...
▢️ mapped connectivity of nucleosomes in S. cerevisiae
▢️ chromatin is predominantly organized into regularly spaced nucleosome arrays
▢️ metaphase chromosomes packed by arrayed cohesin hubs

16.11.2024 16:37 πŸ‘ 40 πŸ” 15 πŸ’¬ 1 πŸ“Œ 0
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The single-molecule accessibility landscape of newly replicated mammalian chromatin By developing a long-read sequencing method to simultaneously map replication status and protein-DNA contacts in cells, Ostrowski, Yang, etΒ al. show that newly replicated chromatin is enriched for unw...

The latest from our group, led by Megan Ostrowski and @martyyang.bsky.social, is now published in final form (www.cell.com/cell/fulltex...! Many thanks to our excellent peer reviewers for suggesting several experiments (including CAF-1 perturbation) to really improve the study =) #epigenetics

15.11.2024 15:35 πŸ‘ 207 πŸ” 75 πŸ’¬ 14 πŸ“Œ 9