Thanks for the invite Joaquin 😊
It was so nice to discuss with everyone and hear about the exciting science happening at the Biozentrum!

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!!)

It's so nice when 2 stories can complement each other beautifully!! 😄
cooperation >>> competition 👭🪰🐭

Thanks Christa! Looking forward to discussing the details in a couple of months 🙂

you must check out @yghavi.bsky.social and @mmasoura.bsky.social's story, who found a similar mechanism in Drosophila. it's so cool if two works align!!

www.biorxiv.org/content/10.1...

Merci Alexis 😄

Thanks Joaquin!

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

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!

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...

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.

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".

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.

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.

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.

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.

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!

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.