Elphege Nora Lab at UCSF
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elphegenoralab.bsky.social
Elphege Nora Lab at UCSF
@elphegenoralab.bsky.social
Our laboratory seeks to understand how chromosome structure relates to genome functions
Pinned
New preprint with @gfudenberg.bsky.social

We find the rate of cohesin loop extrusion in cells is set by NIPBL dosage and tunes many aspects of chromosome folding.

This provides a molecular basis for NIPBL haploinsufficiency in humans. 🧵👇

www.biorxiv.org/content/10.1...
NIPBL dosage shapes genome folding by tuning the rate of cohesin loop extrusion
Cohesin loop extrusion is a major driver of chromosome folding, but how its dynamics are controlled to shape the genome remains elusive. Here we disentangle the contributions of the cohesin cofactors ...
www.biorxiv.org
Reposted by Elphege Nora Lab at UCSF
Very nice Preview by @bramkamplab.bsky.social on the SMC DNA loading paper by our @roisnehamelinf.bsky.social

"Weaving the loops of life: DNA loading by loop-extrusion machines in plasmid defense and genome organization"

Molecular Cell www.cell.com/molecular-ce...
November 6, 2025 at 6:41 PM
Reposted by Elphege Nora Lab at UCSF
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.
November 5, 2025 at 5:20 PM
Hi Genome Engineering peeps!

When you genotype crude cell lysates after colony picking, which PCR enzyme/buffer composition works best for you for genotyping >1.5kb amplicons?

KOD Xtreme is amazingly robust but so $$$😬

Thank you!
October 28, 2025 at 5:23 PM
Reposted by Elphege Nora Lab at UCSF
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....
October 27, 2025 at 11:49 AM
Reposted by Elphege Nora Lab at UCSF
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 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...
www.nature.com
October 21, 2025 at 9:43 AM
Reposted by Elphege Nora Lab at UCSF
Our collab w. V Goel, @nicholas-aboreden.bsky.social , J Jusuf, G Blobel, L Mirny, @irate-physicist.bsky.social out in @natsmb.nature.com www.nature.com/articles/s41...

Was co-submitted with @allanaschooley.bsky.social @jobdekker.bsky.social whose paper should also come out soon

Brief thread 👇
October 20, 2025 at 6:36 PM
Reposted by Elphege Nora Lab at UCSF
The TArgeted Cohesin Loader (TACL) paper was just published. Happy that we were able to contribute to this really exciting project!

If you want to learn how targeting cohesin to defined loci in the genome affects the local chromatin environment and transcription, look no further!

rdcu.be/eLiT5
Characterization of induced cohesin loop extrusion trajectories in living cells
Nature Genetics - This study introduces a system called TArgeted Cohesin Loader (TACL) that recruits cohesin complexes at defined genomic regions and induces loop extrusion events in living cells,...
rdcu.be
October 16, 2025 at 8:17 PM
Reposted by Elphege Nora Lab at UCSF
Ever wondered what drives enhancer-promoter specificity? Why would an enhancer activate one gene rather than another neighboring one?

Check our latest preprint, led by @mmasoura.bsky.social, to find out!
www.biorxiv.org/content/10.1...
Promoter-proximal gatekeepers restrict pleiotropic enhancer inputs to achieve tissue specificity
Developmental enhancers are central regulatory elements that can activate multiple genes, yet how they selectively regulate one gene over its neighbours remains unclear. Using the Drosophila twist E3 ...
www.biorxiv.org
October 16, 2025 at 12:34 PM
Reposted by Elphege Nora Lab at UCSF
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...
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...
www.biorxiv.org
October 16, 2025 at 3:06 PM
Reposted by Elphege Nora Lab at UCSF
How do SMC complexes load onto DNA to get ready for loop extrusion?

@roisnehamelinf.bsky.social & co discovered that Wadjet, an SMC complex involved in bacterial DNA immunity, performs some impressive molecular gymnastics 🤸‍♂️🤸‍♂️🤸‍♂️.

Check out the new paper: www.cell.com/molecular-ce...
October 9, 2025 at 2:43 PM
Reposted by Elphege Nora Lab at UCSF
⚠️ 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
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.
www.nature.com
October 6, 2025 at 1:02 PM
Reposted by Elphege Nora Lab at UCSF
Today I am so pleased to present our work on how chromatin remodelers affect mesoscale chromatin organization.
www.science.org/doi/10.1126/...
ATP-dependent remodeling of chromatin condensates reveals distinct mesoscale outcomes
Adenosine triphosphate (ATP)–dependent chromatin remodeling enzymes mobilize nucleosomes, but how such mobilization affects chromatin condensation is unclear. We investigate effects of two major remod...
www.science.org
October 2, 2025 at 10:55 PM
Reposted by Elphege Nora Lab at UCSF
📣 New preprint from the lab - Endogenous fluctuations of transcription factor levels shape their occupancy in unexpected ways
www.biorxiv.org/content/10.1...
Endogenous variability in transcription factor concentrations shapes their genome-wide occupancy
The control of transcription factor (TF) concentrations is crucial for the precise regulation of gene expression and cell fate decisions during development. Yet, TF concentrations can display substant...
www.biorxiv.org
September 26, 2025 at 8:12 AM
How do enhancers activate genes?

Confused about how cohesin contributes?

Physics uncovers a molecular scenario that explains the biological data across labs

Truly exciting findings from @lucagiorgetti.bsky.social 💪
Really excited to share our latest work led by @mattiaubertini.bsky.social and @nesslfy.bsky.social: we report that cohesin loop extrusion creates rare but long-lived encounters between genomic sequences which underlie efficient enhancer-promoter communication.
www.biorxiv.org/content/10.1...
A🧵👇
September 25, 2025 at 2:06 AM
Reposted by Elphege Nora Lab at UCSF
Really excited to share our latest work led by @mattiaubertini.bsky.social and @nesslfy.bsky.social: we report that cohesin loop extrusion creates rare but long-lived encounters between genomic sequences which underlie efficient enhancer-promoter communication.
www.biorxiv.org/content/10.1...
A🧵👇
September 24, 2025 at 9:45 PM
Reposted by Elphege Nora Lab at UCSF
Really enjoyed reading the new @lucagiorgetti.bsky.social lab preprint that makes the case that not all E-P interactions are created equal - it is the subset of long-lived extrusion-mediated E-P interactions that are most transcriptionally important:
www.biorxiv.org/content/10.1...
September 24, 2025 at 7:08 PM
Reposted by Elphege Nora Lab at UCSF
Excited to share our first preprint! We developed an image-based pooled screen to uncover regulators of HP1 condensates and discovered a link with intronic RNA and RNA processing. 👏 Congrats to all authors, especially Matthew, Shaopu & Chris!
An image-based CRISPR screen reveals splicing-mediated control of HP1α condensates https://www.biorxiv.org/content/10.1101/2025.09.21.676939v1
September 22, 2025 at 7:05 PM
Reposted by Elphege Nora Lab at UCSF
Some (+)ve news to lighten another heavy weekend: our latest preprint (c/o Mattiroli + Ramani labs) is up!
www.biorxiv.org/content/10.1...
A tour-de-force by 1st authors Bruna Eckhardt & @palindromephd.bsky.social, focusing on chromatin replication. RTs welcome; tweetorial in 3,2...(1/n)
The eukaryotic replisome intrinsically generates asymmetric daughter chromatin fibers
DNA replication is molecularly asymmetric, due to distinct mechanisms for lagging and leading strand DNA synthesis. Whether chromatin assembly on newly replicated strands is also asymmetric remains un...
www.biorxiv.org
September 20, 2025 at 4:10 PM
Reposted by Elphege Nora Lab at UCSF
✨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/...
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...
www.science.org
September 19, 2025 at 2:09 PM
Reposted by Elphege Nora Lab at UCSF
Excited to share another new preprint from our lab in which we developed a cluster-based phasing strategy using long read nano-NOMe-seq data to link distinct CTCF binding states—captured at the single molecule level—to the transcriptional status of genes: biorxiv.org/content/10.1...
September 9, 2025 at 5:44 PM
Reposted by Elphege Nora Lab at UCSF
We’re back! Registration is NOW OPEN for the 6th Annual Meeting on Advances in Nuclear Topology & 3D Chromatin Architecture in Cancer. Don’t miss insights from leading experts in the field. Join us online on Nov 25, 2025—register for free: bit.ly/chromatin-2025 #chromatin2025
September 3, 2025 at 2:00 PM
Reposted by Elphege Nora Lab at UCSF
Excited to share our preprint w/Gordana Wutz, Iain Davidson, Leonid Mirny, Jan-Michael Peters
www.biorxiv.org/content/10.1...
Evidence that PDS5A/B limits NIPBL-cohesin life w/effects on CTCF boundaries & chrm compartments, +mechanisms of compartment-extrusion interplay & cohesin regulation by PDS5
PDS5 proteins control genome architecture by limiting the lifetime of cohesin-NIPBL complexes
Cohesin-NIPBL complexes extrude genomic DNA into loops that are constrained by CTCF boundaries. This process has important regulatory functions and weakens the separation between euchromatic and heter...
www.biorxiv.org
September 3, 2025 at 4:20 PM
Excitingly, the lab of Jan-Michael Peters just reported
largely concordant findings:

The PDS5:NIPBL balance in cells tunes the rate/velocity of cohesin loop extrusion, shaping chromosomes from loops to compartments 🚅➰

www.biorxiv.org/content/10.1...
August 31, 2025 at 10:31 PM
Reposted by Elphege Nora Lab at UCSF
In Brief: A new center in San Francisco will offer tailor-made CRISPR therapies to cure children with rare diseases www.nature.com/articles/s41...
Children with rare genetic diseases get CRISPR Cures center - Nature Biotechnology
Nature Biotechnology - Children with rare genetic diseases get CRISPR Cures center
www.nature.com
August 26, 2025 at 4:04 PM
Reposted by Elphege Nora Lab at UCSF
Histone Acetylation Differentially Modulates CTCF-CTCF Loops and Intra-TAD Interactions https://www.biorxiv.org/content/10.1101/2025.07.29.667515v1
August 1, 2025 at 8:33 PM