Elphege Nora Lab at UCSF
@elphegenoralab.bsky.social
1.2K followers 170 following 87 posts
Our laboratory seeks to understand how chromosome structure relates to genome functions
Posts Media Videos Starter Packs
elphegenoralab.bsky.social
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 💪
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🧵👇
Reposted by Elphege Nora Lab at UCSF
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🧵👇
Reposted by Elphege Nora Lab at UCSF
andersshansen.bsky.social
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...
Reposted by Elphege Nora Lab at UCSF
serenasanulli.bsky.social
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!
biorxiv-genetic.bsky.social
An image-based CRISPR screen reveals splicing-mediated control of HP1α condensates https://www.biorxiv.org/content/10.1101/2025.09.21.676939v1
elphegenoralab.bsky.social
That was >40 years ago!

So many of John's papers still read incredibly prescient to this day.

Fun fact, John is still around and scheduled to give his faculty talk to my department this Wednesday.
elphegenoralab.bsky.social
As early as 1984 they reported pairwise distances between loci across they could recognize thanks their cytological patterns.

They were already using distance heatmaps, looking at contact between heterochromatin & the periphery and making polymers models, all with data from single live cells (!)
elphegenoralab.bsky.social
Not sure that's what you want but group of John Sedat was mapping polytene chromosome folding in the mid-80s.

www.nature.com/articles/308...
rupress.org/jcb/article/...
Reposted by Elphege Nora Lab at UCSF
Reposted by Elphege Nora Lab at UCSF
janeskok.bsky.social
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...
Reposted by Elphege Nora Lab at UCSF
janeskok.bsky.social
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
Reposted by Elphege Nora Lab at UCSF
irate-physicist.bsky.social
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
elphegenoralab.bsky.social
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...
Reposted by Elphege Nora Lab at UCSF
biorxiv-genomic.bsky.social
Histone Acetylation Differentially Modulates CTCF-CTCF Loops and Intra-TAD Interactions https://www.biorxiv.org/content/10.1101/2025.07.29.667515v1
elphegenoralab.bsky.social
29 / and this one illustrates the dramatic differences in loop dynamics after depleting
NIPBL (slow rate, normal lifetime)
WAPL (very high lifetime)
PDS5 (high lifetime, high rate)
elphegenoralab.bsky.social
28/ and some movies!

This one illustrates the difference in loop dynamics between high lifetime v.s. high rate, at equal processivity.

LEFT - High lifetime: loops take time to grow but remain for very long

RIGHT - High rate: loops grow super fast but eventually dissociate to reform
Reposted by Elphege Nora Lab at UCSF
dewitlab.bsky.social
We all know that cancers -even from the same subtype- are highly heterogeneous right? In a new study we asked whether this was also the case for the three-dimensional organization of the genome in breast cancer. The answer: it’s complicated. www.cell.com/iscience/ful...
A 3D genome compendium of breast cancer progression
Genomics; Chromosome organization; Molecular Genetics; Cancer
www.cell.com
elphegenoralab.bsky.social
26/ This was a hand in hand collaboration between experimentalists in our group, led by @rini-shah.bsky.social ocial, and physicists in @gfudenberg.bsky.social ’s lab, led by Max Tortora, with help from @nesslfy.bsky.social in @lucagiorgetti.bsky.social ’s lab.
elphegenoralab.bsky.social
25/ There is more in the manuscript 📖 - including

▶️ calibration of models to experiments
▶️ how to titrate & measure chromatin bound cohesin
▶️ how extrusion rate affect compartmentalization & transcription
▶️ speculations about cell types that change expression levels of cohesin co-factors 💭
elphegenoralab.bsky.social
24/ On the other hand, quantitative titrations showed that extrusion rates scale with NIPBL dosage 📐

This is a whole new way to think about the molecular origin of NIPBL haploinsufficiency in Cornelia de Lange patients, who suffer from partial reduction of NIPBL levels.