Update: scE2G is now online at Nature Genetics! Since the preprint, we added a new benchmark on a fully held-out CRISPR dataset. scE2G continues to show state-of-the-art performance, reinforcing that it generalizes well nature.com/articles/s41588-026-02695-8 1/

Jesse Engreitz@jengreitz.bsky.social · 2y ago

Introducing scE2G: a new model to link enhancers to target genes using single-cell data. Excited that scE2G will enable building enhancer maps in hundreds of cell types in the human body! Wonderful collaboration with @randersson.bsky.social @613weilin.bsky.social @mayayayas.bsky.social Thread👇

Together with Hans Bjornsson (and @kasperdhansen.bsky.social, and others) we have spent many years thinking about the molecular basis of Mendelian disorders caused by variants in chromatin regulators. We have written a review where we discuss our thoughts: www.tandfonline.com/doi/full/10....

Mendelian disorders of the epigenetic machinery: a decade of insights into the molecular basis

The Mendelian disorders of the Epigenetic Machinery (MDEMs), or Chromatinopathies, are now understood to be a collectively common cause of childhood neurodevelopmental delays and intellectual disab...

tandfonline.com

Pleased to talk about two related papers from our lab this Spring in GENETICS @genetics-gsa.bsky.social. These two studies are each the work of graduate students in my lab, with contributions from our colleagues. I will describe our system first and then each of the studies /1

Although cohesin-sensitive, long-range enhancer activation is equivalent in nature to proximal activation. Cooperativity can arise from different levels of activation inputs operating on a non-linear response function. @eliasfriman.bsky.social @uoe-igc.bsky.social www.biorxiv.org/content/10.6...

definitely not AI generated

ChromSMF preprint is out!🚀 tinyurl.com/ChromSMF We often piece together chromatin regulation layer by layer from separate assays. But this can be limiting! In @arnaudkr.bsky.social's lab, we developed a method to directly study multiple layers on the same DNA molecule! 🧬 What does this unlock? ⬇️

In collab w @hdashnow.bsky.social, we have a new preprint out on tandem repeat (TR) mutagenesis! Using HiFi sequencing, we profiled nearly 8 million TR loci across four generations of a large CEPH/Utah family and identified 1,270 de novo expansions and contractions. www.biorxiv.org/content/10.6...

Very happy to share our work with Seth Berger and UCI-GREGoR at @ajhgnews.bsky.social . We developed and extensively evaluated a method - duoNovo - that uses long-read sequencing to detect de novo variants using *only one* biological parent. (1/n) R package: github.com/sbergercnmc/...

The American Journal of Human Genetics@ajhgnews.bsky.social · 5mo ago

🧬 New from @leandrosboukas.bsky.social & co 📄Identification of de novo variants from parent-proband duos via long-read sequencing 🖥️ github.com/sbergercnmc/...

A reminder that we are actively recruiting a geneticist to the Department of Genetics at Albert Einstein College of Medicine careers-einstein.icims.com/jobs/17847/a...

Sad to hear of David Botstein's passing. I got into Genomics after attending the famous Bar Harbor course at Jackson Labs in 2013. Botstein was the senior lecturer that year. He had an incredible presence throughout those two weeks, (1/n)

A new preprint out with Shamil Sunyaev. We talk about GWAS, gene expression, evolution, and why searching for trait-associated eQTLs is easier in cattle and pigs. www.biorxiv.org/content/10.6...

Please share this with your network: Postdoctoral position available in my group. www.linkedin.com/jobs/view/43...

Very important work to reconcile canonical transcription initiation structures with the promoter diversity occurring in vivo. Some explanation on how the large majority of our promoters (TATA-less) ma initiate transcription through contacts downstream of the TSS.

Zeitlinger Lab@zeitlingerlab.bsky.social · 7mo ago

The @zeitlingerlab.bsky.social is pleased to announce @sergio-gma91.bsky.social’s preprint “High-resolution binding data of TFIID and cofactors show promoter-specific differences in vivo” (www.biorxiv.org/content/10.6...). TLDR; TFIID behaves differently depending on promoter type. More below:

An early Christmas present for those interested in chromatin and transcription! Fantastic work from @au-ho-yu.bsky.social and @aleksszczurek.bsky.social . Thanks to Inge and Michiel for their help. Please repost! www.biorxiv.org/content/10.6...

SET1/MLL complexes control transcription independently of H3K4me3

Histone H3 lysine 4 trimethylation (H3K4me3) at gene promoters is thought to play a central role in gene transcription. H3K4 methylation is deposited by the SET1 (A/B) and MLL (1-4) multi-protein comp...

biorxiv.org

Massive single-cell study by Kanai et al (www.medrxiv.org/content/10.1...): - Once statistical power is high, constrained genes have more (though weaker) eQTLs. - Chromatin-QTLs near constrained genes have "normal" effect sizes, colocalize more with disease, but exhibit attenuated peak-gene effects.

Do you have an exciting new chromatin/transcription story that you'd like to share with the #FN community? Fill out this form to be considered for a talk in our Jan-June 2026 schedule! forms.gle/TBi38UgYxPAB... Please repost and share!

Application to speak in the Fragile Nucleosome series

Thank you for your interest in our seminar series! We use a variety of different session formats but, in general, trainees can plan for a ~15 min talk + 5min Q/A and PIs can plan for a ~25min talk +...

forms.gle

Excited to share this preprint from first author Jon Rosen, a postdoctoral fellow in the @klmohlke.bsky.social lab and my lab. We examine eQTL study sample size and how this affects signal discovery and rates of colocalization with GWAS. www.biorxiv.org/content/10.1...

Higher eQTL power reveals signals that boost GWAS colocalization

Expression quantitative trait locus (eQTL) studies in human cohorts typically detect at least one regulatory signal per gene, and have been proposed as a way to explain mechanisms of genetic liability...

biorxiv.org

It's publication day, and Cold Spring Harbor Laboratory Press is running a promotion bundling the hard cover and e-book, and other offers: cshlpress.com/default.tpl?... #EpigeneticsBook

John Greally@greally.bsky.social · 10mo ago

My book on Epigenetics: History, Molecules and Diseases www.amazon.com/Epigenetics-... #EpigeneticsBook #Epigenetics

Looking forward to presenting duoNovo at ASHG this week. We use long-read sequencing to detect de novo variants without having to sequence both parents. It's conceptually straightforward, and performs very accurately among variants likely to be clinically relevant. www.medrxiv.org/content/10.1...

Identification of de novo variants from parent-proband duos via long-read sequencing

While de novo variants cause many Mendelian disorders, their detection currently requires sequencing of the proband and both biological parents. This is not feasible when only one parent is available,...

medrxiv.org

One of the greats of 20th century biology. What a life. www.youtube.com/watch?v=v9Em...

David Baltimore

YouTube video by InfiniteHistoryProject MIT

youtube.com

This looks like a creative use of transformers. Looking forward to diving into this. arxiv.org/abs/2508.04111

Negative binomial regression and inference using a pre-trained transformer

Negative binomial regression is essential for analyzing over-dispersed count data in in comparative studies, but parameter estimation becomes computationally challenging in large screens requiring mil...

arxiv.org

My book Epigenetics: History, Molecules and Diseases will be published in exactly one month (September 2). Finalizing cover (looks great), probably going to printer this week. Nervous anticipation is the mood right now.

#apaperaday is back from holiday. Yuzu is still with the birbsitter so a holiday picture it is. Today's pick is from @nejm.org by Musunuru et al on an N=1 case (patient with severe metabolic disease) treated by base editing (CRISPR therapy). DOI: 10.1056/NEJMoa2504747 Very good way to restart!

This week's genome editing triumph is a big deal. Here's why erictopol.substack.com/p/the-first-...

Reminded of Ed Yong’s response to this question: “If I cover a preprint, I talk to 2-3 experts to get their views before writing the story. That’s exactly what I do if I cover a journal article…”

Nicholas Bauer PhD@bioturbonick.net · last yr.

Absolutely. Preprints are for communicating among scientists. If a journalist wants to cover one, they should commission a peer review.

Looking forward to this next week

FragileNucleosome@fnucleosome.bsky.social · last yr.

Join us on Wednesday next week for two exciting talks on transcription regulation from @kasitc.bsky.social and @davidsuter.bsky.social! You can register at: us06web.zoom.us/webinar/regi...

Beautiful combination of population-scale genetic analyses and mouse work. Damaging variants in a highly constrained chromatin remodeler (CHD1) are better tolerated in males, with mouse experiments indicating a protective effect of androgens.

medRxivpreprint@medrxivpreprint.bsky.social · last yr.

Androgens mediate sexual dimorphism in Pilarowski-Bjornsson Syndrome https://www.medrxiv.org/content/10.1101/2025.05.06.25326635v1

Out in Cell @cp-cell.bsky.social: Design principles of cell-state-specific enhancers in hematopoiesis 🧬🩸 screen of fully synthetic enhancers in blood progenitors 🤖 AI that creates new cell state specific enhancers 🔍 negative synergies between TFs lead to specificity! www.cell.com/cell/fulltex... 🧵

Design principles of cell-state-specific enhancers in hematopoiesis

Screen of minimalistic enhancers in blood progenitor cells demonstrates widespread dual activator-repressor function of transcription factors (TFs) and enables the model-guided design of cell-state-sp...

cell.com

Check this out - the company I co-founded is trying to figure out how to make this super easy product.synthesize.bio (and we have beta models out to AI generate new expression data based on experimental design!)

+1 Anshul Part of this means reviewers not ripping on manuscripts that explicitly mention limitations *for those limitations*