Luca Giorgetti lab @FMI
lucagiorgetti.bsky.social
Luca Giorgetti lab @FMI
@lucagiorgetti.bsky.social
We study transcriptional regulation and chromosome folding using an interdisciplinary approach combining wet- and dry-lab methods.
https://giorgettilab.org
@fmiscience.bsky.social
Pinned
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🧵👇
And this is a fantastic result too
(23) If you move SRR2 further than ~20kb from the Sox2 promoter, it cannot support cohesin-independent action of the distal enhancer.

~20kb was the cuttof we say at Car2 for cohesin-independent action of enhancers. Makes sense!
November 28, 2025 at 11:54 AM
Reposted by Luca Giorgetti lab @FMI
(23) If you move SRR2 further than ~20kb from the Sox2 promoter, it cannot support cohesin-independent action of the distal enhancer.

~20kb was the cuttof we say at Car2 for cohesin-independent action of enhancers. Makes sense!
November 27, 2025 at 9:59 PM
This is a fantastic result!
(22) Strikingly, you can replace SRR2 with other weak enhancers to restore cohesin-independence at Sox2

> SRR2 is not special
> proximal and distal elements likely generally synergize in a cohesin-independent way

(thank you @chribue.bsky.social for highlighting the Map4k3 E2 enhancer!)
November 28, 2025 at 11:54 AM
Reposted by Luca Giorgetti lab @FMI
The hinge bypass gate paper is finally out! doi.org/10.1038/s414...

We show how loop-extruding SMC complexes can maintain DNA entrapment while bypassing obstacles on DNA — including transcription machinery & potentially other SMCs.

A lucky convergence of 3 projects lead to the initial discovery!
The SMC Hinge is a Selective Gate for Obstacle Bypass - Nature Communications
SMC complexes are ring-shaped motors that fold DNA by extruding loops, but how they navigate large DNA obstacles is unclear. Here, Liu et al., show that SMC complexes bypass obstacles by threading obs...
doi.org
November 25, 2025 at 3:26 PM
Reposted by Luca Giorgetti lab @FMI
📣 SAVE THE DATE
Next X-inactivation meeting in Sapporo, Japan, 19-23 October 2026. Visit x-inactivation-meeting.org to join our mailing list. 🧬 speakers @dandergassen.bsky.social @marnieblewitt.bsky.social @heard65.bsky.social @crougeulle.bsky.social @sexchrlab.bsky.social @zhouqi1982.bsky.social
November 17, 2025 at 11:39 AM
Reposted by Luca Giorgetti lab @FMI
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 Luca Giorgetti lab @FMI
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 Luca Giorgetti lab @FMI
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 Luca Giorgetti lab @FMI
We are recuiting two new Associate Professors here in Oxford Biochemistry. Come join us! Reach out to me if you have any questions. Please repost! tinyurl.com/mr3m7bd3
October 17, 2025 at 2:56 PM
Reposted by Luca Giorgetti lab @FMI
Come join us in Geneva for everything epigenetics and gene regulation. It will be a great meeting! Please repost!
www.keystonesymposia.org/conferences/...
Epigenetics and Gene Regulation in Health and Disease: Linking Basic Mechanisms with Therapeutic Opportunities | Keystone Symposia
Join us at the Keystone Symposia on Epigenetics and Gene Regulation in Health and Disease: Linking Basic Mechanisms with Therapeutic Opportunities, March 2026, in Geneva, with field leaders!
www.keystonesymposia.org
October 17, 2025 at 2:36 PM
Reposted by Luca Giorgetti lab @FMI
⚠️ 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 Luca Giorgetti lab @FMI
Join us at the Hubrecht Institute in Utrecht to start your research group! Fantastic scientific environment, strong support, and nice colleagues :) Apply and please share broadly in your network.
Ready to establish your own research group at the Hubrecht Institute for Molecular and Developmental Biology? We’re seeking a tenure-track group leader to develop an innovative research line within our vibrant scientific community. Learn more & apply! https://f.mtr.cool/jncxfqkuds
September 28, 2025 at 9:43 AM
Reposted by Luca Giorgetti lab @FMI
The latest work from ours and @vram142.bsky.social lab is out! True teamwork to visualize nascent chromatin with strand resolution, using a fully reconstituted system. Very proud of superstar-PhD student Bruna, and @palindromephd.bsky.social. Learning so much from Vijay’s amazing technologies! RT
September 21, 2025 at 7:12 AM
Reposted by Luca Giorgetti lab @FMI
1/ 🧵 I am excited to share a new preprint from our group:
Single-cell Dam&T-seq during mouse corticogenesis reveals how genome–lamina interactions regulate long neuronal genes.
doi.org/10.1101/2025...
#Neurodevelopment #Epigenetics @hubrechtinstitute.bsky.social @oncodeinstitute.bsky.social
MeCP2 binding and genome–lamina reorganization precede long gene activation during mouse corticogenesis
During corticogenesis, neural gene expression is tightly coordinated by chromatin and epigenetic changes, whose misregulation can lead to neurodevelopmental disorders[1][1]–[4][2]. The role of spatial...
doi.org
September 17, 2025 at 8:41 AM
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 Luca Giorgetti lab @FMI
New work from my lab with the Brown lab on how genome folding changes during motor neuron maturation, and how this process goes awry in ALS motor neurons. Led by Dr. Ozgun Uyan.
www.biorxiv.org/content/10.1...
Dynamic changes in chromosome and nuclear architecture during maturation of normal and ALS C9orf72 motor neurons
We have investigated changes in chromosome conformation, nuclear organization, and transcription during differentiation and maturation of control and mutant motor neurons harboring hexanucleotide expa...
www.biorxiv.org
September 23, 2025 at 9:13 PM
Reposted by Luca Giorgetti lab @FMI
Another FMI Annual Meeting is in the books! After a night of follies and plenty of dancing, today brought the announcement of our internal prize winners, more inspiring talks, and a vibrant poster session. Already looking forward to next year! 🙌
September 17, 2025 at 11:57 AM
Reposted by Luca Giorgetti lab @FMI
📣The Turco group is seeking a computational biologist to analyze large omics datasets. Work on cutting-edge 3D organoid models of the human placenta and be embedded in our Computational Biology Platform (part of @sib.swiss). Apply here: www.fmi.ch/education-ca...
September 12, 2025 at 7:02 AM
Reposted by Luca Giorgetti lab @FMI
I am excited to announce that we are looking for a Lab Manager @fmiscience.bsky.social in Basel. If you want to be part of a growing team investigating development and tissue formation, and are enthusiastic about helping set up a new lab, please check out the role:

www.fmi.ch/education-ca...
September 14, 2025 at 11:46 AM
Become our colleague at @fmiscience.bsky.social! The FMI is a very special place to start your lab: a vibrant international institute with world-class research groups and facilities, core funding, fantastic trainees, great colleagues😅, and a collegial culture. Get in touch if you're interested!
🚨 We're hiring, please share! The FMI seeks a tenure-track Group Leader (Assistant Prof) in Structural Biology 🔬
Innovative scientists in genome regulation, RNA metabolism, or protein homeostasis—especially using cutting-edge approaches—apply now at www.fmi.ch/education-ca...
September 8, 2025 at 8:41 AM
Reposted by Luca Giorgetti lab @FMI
This is not a HiC map! Ever wondered if multiple enhancers get activated simultaneously? We measured chromatin accessibility on thousands of molecules by nanopore to create genome-wide co-accessibility maps. Proud of @mathias-boulanger.bsky.social @kasitc.bsky.social Biology in the thread👇
August 18, 2025 at 1:00 PM
Reposted by Luca Giorgetti lab @FMI
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
August 16, 2025 at 3:03 AM
Reposted by Luca Giorgetti lab @FMI
We are hiring a scientist to lead our 'Build' team at the Seattle Hub for Synthetic Biology. @alleninstitute.org

Job posting below:
alleninstitute.org/careers/jobs...

Please reach out if you have any questions!
Jobs
We are working to solve the biggest mysteries in bioscience.
alleninstitute.org
August 13, 2025 at 7:03 PM
Reposted by Luca Giorgetti lab @FMI
Excited to share the latest work from the lab led by @eharo84.bsky.social, in which we have used synthetic biology to explore the mechanisms by which different types of long-range enhancers ensure robust and precise developmental gene expression

www.biorxiv.org/content/10.1...
Synthetic engineering demonstrates that synergy among enhancers involves an increase in transcriptionally productive enhancer-gene contacts
Enhancers are non-coding cis-regulatory elements that control the expression of distally located genes in a tissue- and time-specific manner. Recent studies indicate that enhancers can differ in their...
www.biorxiv.org
August 11, 2025 at 2:56 PM
Reposted by Luca Giorgetti lab @FMI
We found a new asymmetry in the large-scale chromosome structure: sister chromatids are systematically shifted by hundreds of kb in the 5′→3′ direction of their inherited strands! The work was led by Flavia Corsi, in close collaboration with the Daniel Gerlich lab.
www.biorxiv.org/content/10.1...
1/
July 15, 2025 at 8:11 AM