Jesse Engreitz

The NIH Restructuring Congress Rejected Is Happening Anyway (I used Gemini Nano Banana 2 to create this fictional image.)

elizabethginexi.substack.com/p/the-nih-re...

🧬 @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

The impact is already hitting science agencies hard. The NIH—the world's largest public biomedical research funder—has had to rely on leftover stopgap funds.

New grant awards have slowed to a trickle — exacerbating the effects of a record-long shutdown in October.

(h/t @jeremymberg.bsky.social)

White House stalls release of approved US science budgets The US Congress rejected sweeping cuts to science agencies. But the NIH, the NSF and NASA have had their spending slowed.

Congress rejected massive cuts to US science budgets for 2026, but much of the money still isn’t flowing to researchers.

The culprit? The White House Office of Management and Budget (OMB) is quietly slow-walking the release of funds. 🧵👇

New paper alert 🚀 Our organism-wide single-cell ATAC-seq atlas of mammalian aging is now out in @science.org, led by our fantastic graduate student Ziyu Lu from @rockefeller.edu!
www.science.org/doi/10.1126/...

We wrote a perspective "How to build the regulatory genome: a constructionist guide to the cis-regulatory code", out in Development yesterday. Title says it all. Find it here:

journals.biologists.com/dev/article/...

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 🧵👇

Practical utility of sequence-to-omics models for improving the reproducibility of genetic fine-mapping https://www.biorxiv.org/content/10.64898/2026.02.04.703796v1

Yesterday, five-year-old Liam and his dad Adrian were released from Dilley detention center. I picked them up last night and escorted them back to Minnesota this morning.

Liam is now home. With his hat and his backpack.

We mapped the fitness landscape of the 10kb MYC locus using SpRY-Cas9 saturation mutagenesis. 67% of the essential bps are noncoding. So even for a protein coding gene locus, most genetic information may be encoded outside of coding regions.

Does the noncoding genome actually carry more genetic information than coding seqs? Motivated by this question we mutated every bp in the 10kb MYC locus. Results are even more exciting: Decoding the MYC locus reveals a druggable ultraconserved RNA element www.biorxiv.org/content/10.6...

Population-scale sequencing resolves determinants of persistent EBV DNA - Nature Population-scale WGS reveals genetic determinants of persistent EBV DNA, linking immune regulation—especially antigen processing and MHC class II variation—to EBV persistence and heterogeneous di...

Today in @nature.com, we describe how discarded reads in biobank-scale WGS can help resolve the genetic predictors and consequences of Epstein-Barr Virus (EBV) infection.

Wonderful working with @ryandhindsa.bsky.social @sherrynyeo.bsky.social @erinmayc.bsky.social

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

AlphaGenome is out in @nature.com today along with model weights! 🧬

📄 Paper: www.nature.com/articles/s41...

💻 Weights: github.com/google-deepm...

Getting here wasn’t a straight path. We discussed the story behind the model, paper & API in the following roundtable: youtu.be/V8lhUqKqzUc

An NIH source tells me that after this story was published, agency leadership held an emergency meeting about Council approval and is looking for ways to speed up the pipeline.

"Better late than never?" the source says.

What Happens After a Child Is Taken Into ICE Custody? Five-year-old Liam Ramos' detention by ICE has sparked questions about the policies underlying the agency's deportation operations.

ICE has detained at least 3,800 kids under the second Trump administration — more than 500 of whom were under 5 years old.

Children shouldn't be locked up by our government.

Dems Say They Will Block Funding Bill That Includes Money for DHS After Federal Agents Kill Alex Pretti Senate Majority Leader Chuck Schumer said Saturday evening that Democrats would “not...

"Senate Democrats will not provide the votes to proceed to the appropriations bill if the DHS funding bill is included,” Schumer said Saturday evening.

talkingpointsmemo.com/news/democra...

Construction of complex and diverse DNA sequences using DNA three-way junctions - Nature Sidewinder enables high-fidelity DNA assembly by separating the information that guides assembly from the final assembled sequence.

Nature research paper: Construction of complex and diverse DNA sequences using DNA three-way junctions

go.nature.com/4qu2ExZ

New preprint on technologies to scale up CRISPR screens.

We use them to map 665,856 pairwise genetic perturbations and outline a path to comprehensive interaction mapping in human cells.

We also introduce an approach for cloning lentiviral libraries with billions of elements.

Excited to share our latest work in @ajhgnews.bsky.social 🧬📄

We mapped the regulatory landscape of human liver at single-nucleus resolution using snMultiome, connecting genetic variants to the cell-type mechanisms underlying cardiometabolic disease.
www.sciencedirect.com/science/arti...

Committee Releases Conferenced Defense, Homeland Security, Labor, Health and Human Services, Education, and Related Agencies, and Transportation, Housing and Urban Development, and Related Agencies Bi... United States Senate Committee on Appropriations

The conference (agreement between House and Senate) appropriations bill that includes HHS and NIH was released this morning.

www.appropriations.senate.gov/news/majorit...

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Junction-targeting designs limit the application of CRISPR-Cas13d in circular RNA perturbation studies Abstract. Circular RNAs (circRNAs) are RNA molecules formed through the backsplicing of linear exons. Several thousand have been identified, yet relatively

How can we identify circRNAs that might be functional?

Together with @jengreitz.bsky.social, Howard Chang, and team, we found that answering this question is much more challenging than previously thought!

academic.oup.com/nar/article/...

See thread below:

High-resolution binding data of TFIID and cofactors show promoter-specific differences in vivo TFIID is instrumental in recognizing promoter sequences and initiating transcription, yet a cohesive understanding of how this complex interacts with and functions at different promoter types in vivo ...

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:

Thinking about using Cas13 to screen for functional circRNAs?

Think again!

Thread coming soon

High false sign rates in transcriptome-wide association studies Transcriptome-wide association studies (TWAS) are widely used to identify genes involved in complex traits and to infer the direction of gene effects on traits. However, despite their popularity, it r...

How well does TWAS estimate a gene’s direction of effect on a trait? We think of this as an important stress-test for the accuracy of TWAS.

In a new pre-print, we find that TWAS gets the sign wrong around 20-30% of the time!

doi.org/10.64898/202...

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Genome-scale perturb-seq in primary human CD4+ T cells maps context-specific regulators of T cell programs and human immune traits Gene regulatory networks encode the fundamental logic of cellular functions, but systematic network mapping remains challenging, especially in cell states relevant to human biology and disease. Here, ...

Together with @ronghuizhu.bsky.social, we are thrilled to present our new perturb-seq study of 22M primary CD4+ T cells, across donors and timepoints – the result of a decade-long collaboration between the Marson @marsonlab.bsky.social and Pritchard @jkpritch.bsky.social labs 🧵 tinyurl.com/gwt2025

Join @stirlingchurchman.bsky.social,
@moffittlab.bsky.social, @saramostafavi.bsky.social, me and all speakers for the 2026 CSHL meeting Systems Biology: Global Regulation of Gene Expression, March 11-14. Abstract deadline January 9! More infos and registration at meetings.cshl.edu/meetings.asp...

A free, open-access library of high-quality organism illustrations for science communication We create vector graphics of model organisms and emerging biological research organisms to enhance our publications. We’re sharing these editable graphics under a CC0 license for other scientists to...

A free, open-access library of high-quality organism illustrations for science communication

Do transcriptional activators work on any promoter? Our data says no. 🙅‍♂️
Despite driving ~2/3 of mammalian genes, CpG island (CGI) promoters have remained a puzzle. We identified >50 activators that are exclusively compatible with this promoter class. 🧬

Genome-scale perturb-seq in primary human CD4+ T cells maps context-specific regulators of T cell programs and human immune traits https://www.biorxiv.org/content/10.64898/2025.12.23.696273v1

We’re excited to share our new Nature Genetics paper examining the genetic architecture of aortic valve function and aortic stenosis. We used deep learning of cardiac MRI and MTAG to study disease biology long before clinical diagnosis.

nature.com/articles/s41...

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