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MC Gambetta @mcgambetta.bsky.social · 04/05/2026

Hello all, our lab is recruiting a PhD candidate to study how 3D genome folding impacts gene regulation in development. We're located at the Center for Integrative Genomics department of the University of Lausanne, Switzerland. Please email me if interested. #PhDPosition, #PhDOpportunity

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Reposted by MC Gambetta

Genes & Development @genesdev.bsky.social · 17/03/2026

📽️ G&D Tapes 📽️ G&D Author, Ayokunle Araoyinbo, tells us about the compartment-specific roles of Mei2 in yeast RNA regulation and zygotic development. In this issue of #genesdev: ➡️ genesdev.cshlp.org/content/40/5-6/3… Ayokunle Araoyinbo @vjesticalab.bsky.social #translation #yeast

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Reposted by MC Gambetta

Genes & Development @genesdev.bsky.social · 14/08/2025

📽️ G&D Tapes 📽️ G&D Author, Marion Solbach Mouginot tells us about their recent study in #genesdev describing how meta-domains control neuronal gene expression. Learn more here: ➡️ bit.ly/45wGi5M #TAD #chromatin #transcription #neuron #drosophila #3Dgenome

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MC Gambetta @mcgambetta.bsky.social · 04/08/2025

Join us in person or online for the 24th edition of the Gene Regulation Workshop at Uni Lausanne on Sept 1st, with an again fantastic group of speakers 🥳 Edouard Bertrand Antonio Giraldez Phillip Grote @phillipgrote.bsky.social Susan Mango Danny Nedialkova Lucia Strader @luciastrader.bsky.social‬

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MC Gambetta @mcgambetta.bsky.social · 18/04/2025

This work was led by Marion Mouginot, who notably established a locus-specific proteomics approach that identified Lola-I as a meta-loop-associated factor, together with Sahar Hani (supported by Arianna Ravera, UNIL’s image analysis expert!), who uncovered hierarchical meta-loop formation. 👏

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MC Gambetta @mcgambetta.bsky.social · 18/04/2025

Lola-I was, however, only required to form a single meta-domain. This highlights a dichotomy between factors like Lola-I, which may control neuronal fate largely independently of inter-TAD interactions, and structural proteins like Cp190, which may enable ultra-long range gene regulation.

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MC Gambetta @mcgambetta.bsky.social · 18/04/2025

We developed an unbiased proteomics approach (inspired by Baldi..Becker 2018) to identify proteins bound to meta-loop anchors. This identified a specific isoform of the axon guidance protein Longitudinals lacking (Lola-I) as enriched at several meta-loop anchors, in our pull-downs and in vivo.

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MC Gambetta @mcgambetta.bsky.social · 18/04/2025

Many meta-loop anchors coincide with TAD boundaries. We found that a major determinant of TAD boundary formation in flies (called Cp190) is required to form a large fraction of meta-loops, including CTCF-dependent meta-loops.

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MC Gambetta @mcgambetta.bsky.social · 18/04/2025

How do meta-loops form? Most meta-domains contain 2 or more meta-loops, with some of these forming earlier during neurogenesis than the other(s) in the same meta-domain. We found that in many meta-domains, specific meta-loops (often the earlier forming ones) nucleate others.

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MC Gambetta @mcgambetta.bsky.social · 18/04/2025

1 meta-domain we studied contains a meta-loop connecting promoters of Glutamate receptors 1A and 1B. Disrupting the meta-domain uncoupled their co-transcription (similar to Levo..Levine 2022 for intra-TAD loops connecting paralogous gene promoters).

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MC Gambetta @mcgambetta.bsky.social · 18/04/2025

We precisely disrupted 3 independent meta-domains and found transcriptional defects in all 3 cases. 2 meta-domains we studied contain a meta-loop connecting a neuronal gene promoter to a distant intergenic element. Disrupting the meta-domain decreased neuronal gene transcription by 2-to-3-fold.

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MC Gambetta @mcgambetta.bsky.social · 18/04/2025

We recently showed that in fly neurons, specific pairs of TADs megabases apart specifically come together to form meta-domains (Mohana et al. 2023). Within meta-domains, meta-loops connect accessible chromatin peaks present at promoters of specific neuronal genes or in non-coding intergenic DNA.

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MC Gambetta @mcgambetta.bsky.social · 18/04/2025

Our recent paper reports extremely long-range (up to 5.1 Mb 😲) regulation of certain genes in fly neurons and provides new insights into how they form (see short thread below 👇). genesdev.cshlp.org/gca?gca=gene...

genesdev.cshlp.org

A biweekly scientific journal publishing high-quality research in molecular biology and genetics, cancer biology, biochemistry, and related fields

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MC Gambetta @mcgambetta.bsky.social · 13/02/2025

and thank you to the reviewers whose feedback greatly improved the review 😎

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MC Gambetta @mcgambetta.bsky.social · 13/02/2025

Fun to do this with talented Sanyami Zunjarrao in our lab! Thank you @andersshansen.bsky.social and Marcelo Nollmann for including our review in the 2025 Genome Architecture & Expression edition of COGEDE 😀

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MC Gambetta @mcgambetta.bsky.social · 13/02/2025

We highlighted new research from the past two years on examples of long-range gene regulation - within large TADs, across TADs, and across chromosomes - comparing mechanisms in flies and mammals 🪰❤️🐁. www.sciencedirect.com/science/arti...

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Reposted by MC Gambetta

Eric Feigl-Ding @drericding.bsky.social · 01/02/2025

🛑CANCELLED—“Research on Women’s Health” funding website of the NIH.

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MC Gambetta @mcgambetta.bsky.social · 15/11/2024

yes indeed, BEAF-32 mat- zyg- mutants are not happy...

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MC Gambetta @mcgambetta.bsky.social · 15/11/2024

Thank you to the outstanding efforts of notably Anastasiia Tonelli and Pascal Cousin and another great collaboration with Aleksander Jankowski @ajank@mastodon.online 💪

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MC Gambetta @mcgambetta.bsky.social · 15/11/2024

Exciting findings using insulator-seq are: Not all insulator-binding protein sites act as enhancer-blockers. Not all TAD boundaries act as enhancer-blockers. Both a CTCF motif and its surrounding sequence context are essential for enhancer-blocking.

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MC Gambetta @mcgambetta.bsky.social · 15/11/2024

(2) The insulator activity of CTCF binding sites depends on an intact CTCF motif.

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MC Gambetta @mcgambetta.bsky.social · 15/11/2024

Here’s some proof that insulator-seq works: (1) It identifies biologically meaningful insulators in genomic DNA (both known and novel).

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MC Gambetta @mcgambetta.bsky.social · 15/11/2024

That’s right, insulators works on transiently transfected plasmids! This allows us to test the enhancer-blocking activities of up to 1 million DNA test fragments at a time.

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MC Gambetta @mcgambetta.bsky.social · 15/11/2024

Anastasiia Tonelli in the lab established insulator-seq - a massively parallel reporter assay for enhancer-blockers in Drosophila cells

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