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Elphege Nora Lab at UCSF

@elphegenoralab.bsky.social

Our laboratory seeks to understand how chromosome structure relates to genome functions

185 Posts1373 Follower187 Folgt
Jesse Engreitz@jengreitz.bsky.social · 2d ago

Systematic mapping of enhancers, silencers, and topological elements using prime editing deletion screens www.biorxiv.org/content/10.6... Check out our preprint on next-generation tech for mapping distal regulatory effects! We’re excited to help set this up - please get in touch Thread 👇

Systematic mapping of enhancers, silencers, and topological elements with prime editing deletion screens

Noncoding regulatory elements in the human genome can control gene expression through distinct mechanisms, including acting as enhancers, silencers, or topological elements. However, we lack tools to ...

biorxiv.org

Shawn Cai@xshawncai.bsky.social · 2d ago

Have you ever looked at a gene in IGV or a genome browser and wondered “What are all those (ATAC-seq/H3K27ac/CTCF ChIP-seq/…) peaks doing?” 🤔 I’m thrilled to share that we developed a new technology called Swap-seq to answer that exact question. Swap-seq: www.biorxiv.org/content/10.6...

Mir Lab@mirlab.bsky.social · 2d ago

1/ Our paper, “Enhancer binding kinetics explain transcription factor hub formation,” is now published! Here we set out to understand why transcription factors form bright clusters or “hubs” in the nucleus, and whether those hubs actually control gene activity. tinyurl.com/38uf8348

Enhancer binding kinetics explain transcription factor hub formation

Transcription factors (TFs) form dynamic, high-concentration clusters, condensates, or hubs, proposed to increase TF binding frequency at target enhancers. However, how enhancer sequence shapes hub pr...

tinyurl.com

Jessica Mella@jmella.bsky.social · 3w ago

First Bluesky post for my new preprint! Super fun project with guidance from @abbybuch.bsky.social and @willowcoyote.bsky.social. We applied saturation mutagenesis to the Lamin A protein in #hiPSC derived cardiac cells to uncover cell type-specific mutation effects 1/ www.biorxiv.org/content/10.6...

Cardiomyocyte vulnerability to lamin polymer disruption revealed by saturation mutagenesis

Hundreds of mutations to the broadly expressed LMNA gene cause disease primarily within cardiac, muscular, and adipose tissues (1). Tissue-specific pathogenesis arises when mutant protein dysfunction ...

biorxiv.org

Angelika Feldmann@angelikafeldmann.bsky.social · 3w ago

1\ We know a bit about how 3D chromatin interactions are formed, but what do we know about how they are disrupted? We asked this question in our latest preprint: doi.org/10.64898/202..., focusing on the massive loss of promoter interactions during neuronal differentiation.

Developmentally programmed loss of long-range Polycomb interactions is regulated by cohesin

Distal regulatory elements (DREs), such as enhancers, can regulate genes across megabase-long distances, presumably via coming into close spatial proximity. The establishment of new transcriptional programmes during cell type transitions is associated with widespread rewiring of the spatial organisation of the genome, including gain and loss of chromatin interactions. Extensive effort has been invested into understanding how chromatin interactions are formed during development, yet the mechanisms underlying their developmental loss remain largely unclear. By leveraging chromatin accessibility-assisted footprinting, acute protein degradation and chromatin conformation capture, we show that loss of promoter interactions cannot be explained by reduced binding of sequence-specific transcription factors (TFs). Instead, we identify a subset of interactions that depend on cohesin for programmed developmental disruption. These sites are characterized by high Polycomb enrichment and TF occupancy and engage in strong long-range interactions that undergo extensive differentiation-dependent rewiring. Preventing interaction loss by acute cohesin degradation results in the preferential downregulation of associated genes. Together, these results suggest that cohesin indirectly regulates developmental loss of Polycomb interactions by enabling the acquisition of other potentially regulatory contacts in a process that may shape transcriptional programs during cell type transitions. ### Competing Interest Statement The authors have declared no competing interest. European Research Council Helmholtz Society, VH-NG-1604

doi.org

Mark Pownall@mpownall.bsky.social · 4w ago

❗Postdoc positions available! We have multiple fully funded openings in the lab - please reach out if you’re interested. I’ll be at CSHL Epigenetics and Chromatin this week, so come find me if you’d like to learn more about the lab or potential projects

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Vijay Ramani@vram142.bsky.social · 4w ago

Everything you wanted to know about single-molecule epigenomics but were too afraid to ask! Wonderful to co-write (h/t ENORMOUS lift by @arnaudkr.bsky.social) this primer on our nascent field. Also, a 💯 example of wonderful colleagues building something *together*, not in competition =)

A practical guide to studying genome function using single-molecule genomics

Nature Reviews Molecular Cell Biology - Single-molecule genomics methods are used to study the activity of regulatory factors on individual DNA molecules genome-wide, thereby enabling...

nature.com

Hannah Long@hannahlong.bsky.social · last mo.

📣 Interested in non-coding disease-causing variants? Check out our review "Mechanisms underlying disease-causing variants in promoters and enhancers". Interesting mechanisms, challenges and future perspectives. Great to work with @wbickmor.bsky.social, Kun and Ryan! www.nature.com/articles/s41...

Mechanisms underlying disease-causing variants in promoters and enhancers - Nature Genetics

This Review discusses how rare-disease-causing variants in the noncoding genome impact gene regulation, why these examples are so few and how new approaches could accelerate discovery of noncoding var...

nature.com

Wendy Bickmore@wbickmor.bsky.social · last mo.

It was great working with students Kun and Ryan and @hannahlong.bsky.social, combing the literature to try and find examples of bona fide disease-causing variants in non-coding elements - promoters, enhancers and silencers. www.nature.com/articles/s41...

@heardlab.bsky.social · last mo.

New preprint from the Heard Lab and the Marti-Renom lab! 🧬 We show that X-inactivation escapee domains form distinct chromatin compartments independently of CTCF and cohesin. www.biorxiv.org/content/10.6...

X-inactivation escapee domains are CTCF-cohesin independent chromatin compartments

X-chromosome inactivation involves chromosome-wide gene silencing accompanied by extensive chromatin changes, as well the loss of topologically associating domains. Yet discrete regions of the inactiv...

biorxiv.org

Job Dekker@jobdekker.bsky.social · 2mo ago

How do nuclear compartments form inside cell nuclei? We show RNA glues certain loci together to form a nuclear compartment. This involves special GC-rich regions of highly expressed genes that also associate with nuclear speckles, but interactions between these loci are independent of speckles!

bioRxiv Genomics@biorxiv-genomic.bsky.social · 2mo ago

Formation of an RNA-mediated nuclear compartment https://www.biorxiv.org/content/10.64898/2026.08.20.746005v1

Jesse Engreitz@jengreitz.bsky.social · 3mo ago

An encyclopedia of enhancer-gene regulatory interactions — online today! nature.com/articles/s4158… Now with an improved model, expanded maps across 1400+ biosamples, larger validation CRISPR datasets, and guidance on applying the model 1/

nature.com

Andreas Gschwind@argschwind.bsky.social · 3mo ago

Thrilled to share that our ENCODE enhancer–gene mapping paper is now out in Nature! An encyclopedia of human enhancer–gene regulatory interactions: www.nature.com/articles/s41... Thread 👇 1/

Luca Giorgetti lab @FMI@lucagiorgetti.bsky.social · 3mo ago

Our preprint is now out in @natgenet.nature.com ! doi.org/10.1038/s415... We measured Sox2 promoter bursting dynamics with the SCR enhancer positioned at different distances within a genomic locus devoid of confounding effects in mESC: Main findings in the 🧵 below:

Enhancer control of promoter activity and variability via frequency modulation of clustered transcriptional bursts - Nature Genetics

Tünnermann et al. use live-cell imaging to study promoter activity under the control of an enhancer inserted at different genomic distances. RNA production from the promoter occurs in clusters of tran...

doi.org

Luca Giorgetti lab @FMI@lucagiorgetti.bsky.social · 2y ago

Celebrating 10 years of our lab with a new preprint: www.biorxiv.org/content/10.1... How does enhancer location within a TAD control transcriptional bursts from a cognate promoter? Experiments by Jana Tünnermann and modelling by Gregory Roth

Elzo de Wit lab @ NKI@dewitlab.bsky.social · 3mo ago

(1/10) The majority of human genetic variation is located in non-coding regions. The great challenge of the post-genomic era is to assign function to these variants. We reasoned that combining haplotyping with allele-specific multiomics can help pinpoint the functional ones: rdcu.be/fgr5W. A thread:

Mapping functional non-coding variation in individual human genomes through haplotyping, multiomics, and deep learning

Nature Communications - How non-coding mutations in DNA contribute to phenotypes is a largely unresolved question. Here the authors integrate personal genomics and machine learning to identify...

rdcu.be

Jason Tan@yjtan.bsky.social · 3mo ago

Does every enhancer work with every promoter? With @jengreitz.bsky.social and Will Greenleaf, we revisit this long-debated question and resolve an outstanding contradiction in the field. A tour 🧵👇 www.biorxiv.org/content/10.6...

Intrinsic promoter responsiveness dictates sensitivity to transcriptional activation by enhancers

Enhancers activate specific target promoters, but whether intrinsic enhancer-promoter compatibility contributes to this specificity is debated. Recent studies using different reporter assays have reac...

biorxiv.org

Konrad Chudzik@konrad-chudzik.bsky.social · 3mo ago

My first PhD paper is out in Nucleic Acids Research! We describe "Ab-trapping" - an antibody artifact that distorts assays relying on antibody diffusion (microscopy, CUT&Tag, CUT&RUN). The revisions made the story much stronger. Check it out! doi.org/10.1093/nar/...

Antibody-trapping presents a widespread pitfall for microscopy and genomics in the nucleus

Abstract. Chromatin has a complex 3D structure and diverse binding proteins that coordinate the genome’s most essential functions. Many microscopy and geno

doi.org

Anders Sejr Hansen@andersshansen.bsky.social · 3mo ago

Excited to see James' Genome-wide Absolute Quantification of Looping paper out in @natsmb.nature.com : www.nature.com/articles/s41... This has been in collaboration with @lucagiorgetti.bsky.social @leonidmirny.bsky.social @zechnerlab.bsky.social labs. Brief thread below on some key updates

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Anders Sejr Hansen@andersshansen.bsky.social · 2y ago

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...

Vijay Ramani@vram142.bsky.social · 4mo ago

JIT 4 summer, the latest preprint from our lab, brilliantly led by @kaitezhang.bsky.social w/ support from Collepardo lab (@juliamaristany.bsky.social / @janhuemar.bsky.social). www.biorxiv.org/content/10.6... describes a new single-molecule epigenomic method, & discoveries it enables ... (1/n)

Single-molecule nucleosome spacing coordinates chromatin fiber interactions

Nucleosome spacing influences higher-order chromatin fiber organization in vitro but how this relates to cellular chromosome structure remains contentious. To address this, we developed Ligation Analy...

biorxiv.org

Elphege Nora Lab at UCSF@elphegenoralab.bsky.social · 4mo ago

Interested in hearing about mechanisms of cohesin-dependent vs. -independent enhancer regulation? @karissalhansen.bsky.social will be presenting her work **Tues June 23rd 8am CET** www.biorxiv.org/content/10.6... www.science.org/doi/10.1126/... Thank you @genome-org-aus.bsky.social ! 👇

GOA - Genome Organisation Australia@genome-org-aus.bsky.social · 4mo ago

Only one week to go until our next GOA seminar! @karissalhansen.bsky.social will present here work on the mechanisms of long-range enhancer-promoter communication. Registration link: unimelb.zoom.us/webinar/regi...