Abrar Aljahani

Acute NIPBL depletion reveals in vivo dynamics of loop extrusion and its role in transcription activation - Nature Genetics Acute depletion of NIPBL reveals a class of chromatin loops that are independent of NIPBL for their maintenance but not their establishment and that NIPBL is necessary for the expression of lineage-de...

Very excited to share my postdoc research in the @jesserdixon.bsky.social lab at @salkinstitute.bsky.social, out online at @natgenet.nature.com today! www.nature.com/articles/s41... We investigated the function of the cohesin accessory protein NIPBL, making two particularly interesting findings:

A small polymerase ribozyme that can synthesize itself and its complementary strand The emergence of a chemical system capable of self-replication and evolution is a critical event in the origin of life. RNA polymerase ribozymes can replicate RNA, but their large size and structural ...

How could a simple self-replicating system emerge at the origins of life? RNA polymerase ribozymes can replicate RNA, but existing ones are so large that their self-replication seems impossible. Could they be smaller?

Excited to share our latest work in @science.org on a new small polymerase.
1/n

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 🧵👇

🧪🧬New preprint We present cryo-EM structures of reconstituted CTCF–nucleosome complexes, showing CTCF dimerization drives nucleosome oligomerization into defined higher-order assemblies. Disrupting CTCF–CTCF interfaces in mESCs reduces looping and impairs differentiation. tinyurl.com/CTCF-nucleos...

Unique territorial and compartmental organization of chromosomes in the holocentric silkworm - The EMBO Journal Hallmarks of multicellular eukaryotic genome organization are chromosome territories, compartments, and loop-extrusion-mediated structures, including TADs. However, these have mainly been observed in ...

How do compartmentalization & loop extrusion organize eukaryotic genomes beyond classical model organisms?
Hi-C analysis of silkworm chromosomes by Drinnenberg, Muller, Mirny et al reveals new combination of these mechanisms, and a new, secluded “S” compartment
link.springer.com/article/10.1...

Advancing regulatory variant effect prediction with AlphaGenome - Nature AlphaGenome, a deep learning model that inputs 1-Mb DNA sequence to predict functional genomic tracks at single-base resolution across diverse modalities, outperforms existing models in variant effect...

I had intended to post something about this new Google DeepMind paper that appeared yesterday in Nature, but the press coverage has added to what there is to say. So this is a long 🧵
www.nature.com/articles/s41...

Antisense transcription can induce expression memory via stable promoter repression - Genome Biology Background The capacity of cells to retain a memory of previous signals enables acquisition of unique fates and adaptation to their environment. The underlying gene expression memory can arise from mu...

⚠️ The final work of two former PhD students Till @tschwammle.bsky.social and Verena @verenamutzel.bsky.social is out!
➡️⬅️ They dissect how memory can arise from antisense transcription using mathematical modelling 💻, genomics 🧬 and synthetic biology ⚒️! link.springer.com/article/10.1...

Preprint alert: Jiangyuan Liu developed a new workflow for chromatin loop calling across Hi-C datasets, e.g., during differentiation. Most loops are shared between datasets/cell states. Important work for all interested in chromatin loops and how to identify them!

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

If you’ve heard me talk in the past ~5 years, you will know I have developed an obsession with acrocentric chromosomes. This is all of that, condensed into one paper. I will do a full thread in the new year, but for those that want something to read over the holidays, have at it. Such a cool story!

Predictive design of tissue-specific mammalian enhancers that function in vivo in the mouse embryo Enhancers control tissue-specific gene expression across metazoans. Although deep learning has enabled enhancer prediction and design in mammalian cell lines and invertebrate systems, it remains uncle...

Our preprint "Predictive design of tissue-specific mammalian enhancers that function in vivo in the mouse embryo" is on bioRxiv: www.biorxiv.org/content/10.6... . Amazing collaboration by @shenzhichen1999.bsky.social, Vincent Loubiere (@impvienna.bsky.social,@viennabiocenter.bsky.social),... (1/2)

Interphase chromosome conformation is specified by distinct folding programmes inherited through mitotic chromosomes or the cytoplasm - Nature Cell Biology Schooley et al. find that mitotically bookmarked loci drive a transient chromosome folding state during G1 entry that is subsequently modulated by factors inherited through the cytoplasm.

Exciting new paper out! @allanaschooley.bsky.social and Sergey Venev led this project that let to the discovery of two chromosome folding programs: one inherited via mitotic chromosomes and one mitotic inherited through the cytoplasm!

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

Congrats Agnese, beautiful work!

Escape from X inactivation is directly modulated by Xist noncoding RNA Nature Cell Biology - The authors show that increased Xist RNA levels can induce de novo silencing of genes that normally escape X inactivation. SPEN depletion prevents the silencing of escape...

Very happy to share our paper rdcu.be/eUImj out today in @natcellbio.nature.com 🎉🎉🎉
We uncover an unexpected role for endogenous Xist RNA in regulating X-linked genes that escape X-inactivation.

It's always special when you find your own paper in the table of contents of the journal 😍

"The cis-regulatory logic integrating spatial and temporal patterning in the vertebrate neural tube" -> Now out in its final form

www.cell.com/developmenta...

📣 Paper alert!

I am delighted that our paper exploring the impact of Neanderthal-derived variants on the activity of a disease-associated craniofacial enhancer has been published in Development today!
journals.biologists.com/dev/article/...

Repair of DNA double-strand breaks leaves heritable impairment to genome function Upon DNA breakage, a genomic locus undergoes alterations in three-dimensional chromatin architecture to facilitate signaling and repair. Although cells possess mechanisms to repair damaged DNA, it is ...

𝗖𝗮𝗻 𝗰𝗲𝗹𝗹𝘀 𝗲𝘃𝗲𝗿 𝘁𝗿𝘂𝗹𝘆 𝗿𝗲𝗰𝗼𝘃𝗲𝗿 𝗳𝗿𝗼𝗺 𝗗𝗡𝗔 𝗱𝗮𝗺𝗮𝗴𝗲?Excited to share our new study “Repair of DNA double-strand breaks leaves heritable impairment to genome function”, revealing DNA repair’s hidden cost, out now @science.org tinyurl.com/5n6zw3ye. Led by @sbantele.bsky.social and Jiri Lukas.🧵👇1/n

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.

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....

Enhancer activation from transposable elements in extrachromosomal DNA - Nature Cell Biology Kraft, Murphy, Jones et al. identify extrachromosomal DNA (ecDNA)-interacting elements (EIEs) enriched for transposable elements within ecDNA in colorectal cancer cells. They show that EIE 14 integrat...

Here, we show that the unique regulatory landscape of ecDNA enables an ancient LINE to resurrect and act as an enhancer of Myc. This was so fun with @katerinakraft.bsky.social and @mattjones.bsky.social and others. www.nature.com/articles/s41...

Enhancer-promoter compatibility is mediated by the promoter-proximal region Gene promoters induce transcription in response to distal enhancers. How enhancers specifically activate their target promoter while bypassing other promoters remains unclear. Here, we find that the p...

What is a promoter? And how does it work?

We very happy to share our latest work trying to understand enhancer-promoter compatibility.
I am very excited about the results of @blanka-majchrzycka.bsky.social, which changed the way I think about promoters

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

Antiviral reverse transcriptases reveal the evolutionary origin of telomerase Defense-associated reverse transcriptases (DRTs) employ diverse and distinctive mechanisms of cDNA synthesis to protect bacteria against viral infection. However, much of DRT family diversity remains ...

1/10 Genome maintenance by telomerase is a fundamental process in nearly all eukaryotes. But where does it come from?

Today, we report the discovery of telomerase homologs in a family of antiviral RTs, revealing an unexpected evolutionary origin in bacteria.
www.biorxiv.org/content/10.1...

If you’re interested in exploring the relationship between chromatin organization and epigenetic memory using chromatin tracing microscopy, my group is recruiting a talented PhD student 🥳

This is super cool! The implications for future studies are tremendous!

Reporter CRISPR screens decipher cis-regulatory and trans-regulatory principles at the Xist locus - Nature Structural & Molecular Biology Here Schwämmle et al. develop CRISPR reporter screens to map transcription-factor-regulatory element interactions at the Xist locus, revealing a two-step mechanism integrating developmental and X-dosage signals to initiate X-chromosome inactivation.

⚠️ Paper alert: Using a novel CRISPR screening approach, we mapped the entire regulatory network controlling Xist—key for X-chromosome inactivation.
👉 We discover how sex and development signals are decoded at a single gene locus.
www.nature.com/articles/s41...
👇 Bluetorial

Kinetic organization of the genome revealed by ultraresolution multiscale live imaging Genome function requires regulated genome motion. However, tools to directly observe this motion in vivo have been limited in coverage and resolution. Here we introduce an approach to tile mammalian c...

Our Boettiger lab paper on live-cell imaging of DNA motion across genomic scales is out! www.science.org/doi/10.1126/...

Kinetic organization of the genome revealed by ultraresolution multiscale live imaging Genome function requires regulated genome motion. However, tools to directly observe this motion in vivo have been limited in coverage and resolution. Here we introduce an approach to tile mammalian c...

Congrats to my friends in the Boettiger lab for this really beautiful live imaging work. A big leap forward in understanding the dynamic side of genome organization. www.science.org/doi/10.1126/...

Functional maps of a genomic locus reveal confinement of an enhancer by its target gene Genes are often activated by enhancers located at large genomic distances, and the importance of this positioning is poorly understood. By relocating promoter-reporter constructs into thousands of alt...

✨Exciting news: the main story of my PhD is out in Science!

Together with Christine Moene @cmoene.bsky.social, we explored what happens when you scramble the genome—revealing how Sox2’s position shapes enhancer activation.

📖 Read the full story here: www.science.org/doi/10.1126/...

Out today. 🙏 again to everyone for this wonderful piece of work, in particular to Aurelie @aurhin.bsky.social Chase @chasebolt.bsky.social and Brent @homeobox.bsky.social. 🙏 also to the Harris lab @fish4walking.bsky.social and @neilshubin.bsky.social @biology-unige.bsky.social @college-de-france.fr

De-novo promoters emerge more readily from random DNA than from genomic DNA Promoters are DNA sequences that help to initiate transcription. Point mutations can create de-novo promoters, which can consequently transcribe inactive genes or create novel transcripts. We know lit...

Excited / nervous to share the “magnum opus” of my postdoc in Andreas Wagner’s lab!

"De-novo promoters emerge more readily from random DNA than from genomic DNA"

This project is the accumulation of 4 years of work, and lays the foundation for my future group. In short, we… (1/4)

Is euchromatin really “open”? Our new study @bioRxiv suggests otherwise. Using super-resolution imaging @shiori-iida.bsky.social‬ @masaashimazoe.bsky.social reveals: Euchromatin forms condensed domains in live cells. Cohesin constrains them and prevents domain mixing.
www.biorxiv.org/cgi/content/...