Yad Ghavi-Helm
Researcher @CNRS, PI @igflyon.bsky.social, Scientific coordinator #spatialOMICs facility @Spatial_Cell_ID facility @ENSdeLyon #enhancer #transcription #development #3Dgenome #Drosophila
There is a special Current Opinion in Genetics & Development issue about genome architecture and expression and it looks great including reviews by @lennarthilbert.bsky.social @yghavi.bsky.social and @wbickmor.bsky.social www.sciencedirect.com/special-issu...- [Not loaded yet]
- Nice! 🤩
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- Thanks for the invite Joaquin 😊 It was so nice to discuss with everyone and hear about the exciting science happening at the Biozentrum!
- Congratulations to Dr @baalberti.bsky.social !! 🎉 And many thanks to his jury members @randersson.bsky.social @arnausebe.bsky.social @olivier-gandrillon.mastodon.social.ap.brid.gy Marie Sémon Anouck Necsulea and co-supervizor @paulvilloutreix.bsky.social
- This is so cool! It’s also nice to see how careful genetic dissection of loci is still at the forefront of discovery!
- 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...
- Thanks Babis! Indeed, I love it when simple experiments can sometimes just be enough 🤩 Not everything necessarily needs the heavy OMICs weapons 😜 (And this is from someone who loves genomics!!)
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- It's so nice when 2 stories can complement each other beautifully!! 😄 cooperation >>> competition 👭🪰🐭
- A must read! Check out @blanka-majchrzycka.bsky.social and @danielibrahim.bsky.social 's latest work
- 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...
- super cool to see this out! looking forward to now read the details! Congratulations, Yad and @mmasoura.bsky.social
- 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...
- Thanks Christa! Looking forward to discussing the details in a couple of months 🙂
- 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...
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- Merci Alexis 😄
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- Thanks Joaquin!
- To finish, I would like to acknowledge all the members of the lab who made this work possible, in particular @mmasoura.bsky.social, soon to be graduating and on the job market!
- Special thanks also to the continuous support of @erc.europa.eu @agencerecherche.bsky.social @frm-officiel.bsky.social @fondationarc.bsky.social @igflyon.bsky.social @ensdelyon.bsky.social @cnrs.fr
- Altogether, we believe that these promoter-proximal gatekeepers belong to an emerging class of non-canonical regulatory elements that, together with facilitators and other similar elements, can modulate enhancer activity without acting as enhancers themselves.
- Finally, we believe that these elements are not unique to the E3 enhancer or to Drosophila as beautiful work from @blanka-majchrzycka.bsky.social in @danielibrahim.bsky.social lab arrives to similar conclusions at the mouse Sox9 locus. www.biorxiv.org/content/10.1...
- While the "generic" hsp70 core promoter can fully respond to E3's input, the expression of the reporter is restricted when combined with the minimal promoter of each of E3's target genes. This minimal promoter includes a ~100bp region upstream of the core promoter.
- Importantly, this promoter-proximal region does not drive enhancer activity on its own. It only seems to restrict the input of the enhancer. We therefore called it a "gatekeeper".
- If E3 can drive such complex expression, how is each target gene expressed only in a very specific spatio-temporal window then?? We discovered that the answer does not lie in the sequence of the enhancer or in its ability to form enhancer-promoter loops.
- Instead, we found that the promoter-proximal region of each target gene plays a critical role. Indeed, the ability of a reporter gene to respond to E3's input varies drastically depending on the promoter.
- However, to our surprise, we realized that in reporter assays, the activity of E3 is actually much more complex! The enhancer seemed to be active in tissues and stages when twist is not expressed, including non-mesodermal tissues!
- In fact, we realized that E3 is a pleiotropic enhancer that is driving the expression of at least 3 other genes, each expressed in a very different spatio-temporal context.
- Various hypotheses suggested that specificity might have to do with 3D genome organization, the sequence of the core promoter, etc... We now provide evidence that the answer instead lies upstream of the core promoter, in the promoter-proximal region!
- To reach this conclusion, we first had to study an enhancer in great detail. We did this using the E3 enhancer of twist in Drosophila melanogaster embryos. E3 was previously characterized as a mesodermal enhancer driving the expression of the twist gene during early embryogenesis.
- In the starting blocks for #EDRC2025! Come see our work at posters 100 and 155 and during the Gene expression in the 3D nuclear space workshop!
- Actually it’s poster 151 and 241!
- Merci au @cnrsbiologie.bsky.social de mettre en avant notre travail! @baalberti.bsky.social @paulvilloutreix.bsky.social @igflyon.bsky.social @ensdelyon.bsky.social
- Un embryon virtuel pour cartographier l’activité des régions régulatrices du génome 🤝 @yghavi.bsky.social @cnrs-rhoneauvergne.bsky.social 👉 Lire l'article dans @narjournal.bsky.social buff.ly/e41cZQD
- 📢 We are recruiting! Several projects are available and can be tailored to the candidate's profile. Most include confocal imaging/spatial OMICs technologies. Please share and RT 🙏
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- haha me too! Still a long way to go though...
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- Yes! We are now cultivating them in the lab since a couple of months thanks to @criscanestro.bsky.social @evodevogenomeub.bsky.social and have started a very exciting project 🤩
- Now available in its final form @narjournal.bsky.social ! doi.org/10.1093/nar/... Find out how we can reconstruct enhancer activity in vivo in the Drosophila embryo using scRNAseq data and Optimal Transport.
- 🚨Preprint alert! tinyurl.com/2zkmynsd Did you ever dream of reconstruction #spatial single-cell #enhancer activity in a multicellular organism using massively parallel enhancer-reporter assays? Then Spatial-scERA is the method for you! #spatialOMICs
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- Thanks Virginia! Hope you like it 😄
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- Thanks Joaquin!
- This is the work of a talented PhD student @baalberti.bsky.social (on the job market!) together with Séverine Vincent, and a great collaboration with @paulvilloutreix.bsky.social 🙌 @igflyon.bsky.social @cnrsbiologie.bsky.social @ensdelyon.bsky.social
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- Merci Alexis!
- Honored and extremely grateful to see our project in collaboration with @hilaryashe.bsky.social and @hilsawh.bsky.social awarded an #HFSPReseachGrant @hfspo.bsky.social Stay tuned for exciting job offers!
- 🥳Congratulations to the 104 pioneering scientists from 30 nations awarded 2025 #HFSPResearchGrants! 🎉Your frontier research is shaping the future of #LifeSciences! 🌍🔬🧪 🏆 Meet the awardees & their projects: www.hfsp.org/bookletRG202... #ScienceDiplomacy #HFSP #FrontierScience #sts
- Thanks @evodevogenomeub.bsky.social @criscanestro.bsky.social for having us and showing us all the secrets of beautiful Oikopleura!! 😍
- Lovely day at @biom-banyuls.bsky.social So much exciting science on cool marine species!
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- Thanks!!
- 🚨Preprint alert! tinyurl.com/2zkmynsd Did you ever dream of reconstruction #spatial single-cell #enhancer activity in a multicellular organism using massively parallel enhancer-reporter assays? Then Spatial-scERA is the method for you! #spatialOMICs
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- Thanks!
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- 🙋🏽♀️
- On my way to Heidelberg @EMBL #EMBLOmics to present our work. Looking forward!!!
- 🚨Preprint alert! tinyurl.com/2zkmynsd Did you ever dream of reconstruction #spatial single-cell #enhancer activity in a multicellular organism using massively parallel enhancer-reporter assays? Then Spatial-scERA is the method for you! #spatialOMICs
- While we demonstrate the use of spatial-scERA in Drosophila embryos, this method can be applied to screen the single-cell spatiotemporal activity of hundreds of enhancers in parallel in any multicellular organism amenable to transgenesis.
- This work could not have been possible without the support of @ERC_Research @FRM_officiel @AgenceRecherche especially through the "investissement d'avenir" program that funds the @Spatial_Cell_ID facility @ENSdeLyon @igflyon.bsky.social
- Just an example to showcase the power of our method: we could reconstruct the activity pattern of the h_stripe1 enhancer based on the sequencing of our reporter construct in only 9 cells!
- Interestingly, our results highlight that chromatin accessibility is often a poor predictor of enhancer activity. Some of the regions we tested overlapped with highly accessible regions. However these regions are not active in reporter assays!
- Thanks to these innovations, we could greatly improve cell recovery and faithfully reconstruct the spatial activity of enhancers by plotting their probability of presence at each position, even when very few positive cells have been sequenced.
- We applied the method to 25 candidate enhancer regions in stage 6 Drosophila embryos and demonstrated that single-cell enhancer-reporter assays alone are not always sufficient to predict enhancer activity in vivo. In fact, specialization is really essential!
- We combined the principle of MPRAs with single-cell transcriptomics and spatial reconstruction using optimal transport to reconstruct virtual maps of enhancer activity in stage 6 Drosophila embryos. Our method presents 2 key innovations:
- 1) it combines scRNAseq with targeted PCR to improve the identification of cells in which an enhancer is active. 2) it uses a custom version of novoSpaRc, a computational method for spatialization to reconstruct a map of enhancer activity on a virtual embryo.
- Very proud of this huge project led by Baptiste Alberti & Séverine Vincent, together with Isabelle Stevant! Great collaboration with @paulvilloutreix.bsky.social on the computational aspects.
