Thank you @andersshansen.bsky.social and Jamie Drayton for this very nice collaboration and the beautiful RCMC maps 😀

New preprint from our lab!

What can we learn about the properties of gene regulatory elements by CRISPR’ing a random set of accessible sites in human cells?

Find out here: www.biorxiv.org/content/10.1...

👇

1/

For another cool example of what “hopping” can uncover—this time in the context of lamina interactions—check out Lise’s paper: www.nature.com/articles/s41...

@cmoene.bsky.social @nkinl.bsky.social @oncodeinstitute.bsky.social @basvansteensellab.bsky.social

6/ Beyond Sox2, this technology opens the door to studying how genomic location shapes the activity of many different DNA elements in a high-throughput way. We believe it will be broadly useful for diverse biological questions. 🚀

5/ We found that this competition is partly encoded in the Sox2 coding sequence (CDS) – a 1kb exon. Addition of the CDS to the reporter increases reporter expression and competition with the Sox2 gene. This effect seems to be mediated by the CDS-DNA sequence rather than the produced RNA or protein.

4/ Strikingly, deleting the endogenous Sox2 gene expands this landscape—yet the original Sox2 site remains a “sweet spot” for activation. Genes can thus act as gatekeepers, restricting their enhancer’s influence.

3/ These maps depict a sharply confined activation landscape. Interestingly, reporter expression is highest at the enhancer and around the endogenous gene whereas it turns silent upstream of the gene and downstream of the enhancer.

2/ By “loading” our transposon with a fluorescent Sox2 reporter, relocating it, and sorting cells by reporter expression, we generated high-resolution activity maps.

1/ Using a transposon-based approach, we systematically studied the positional relationship between the mouse Sox2 gene and its enhancer (SCR). In a single experiment, we can map >2000 unique genomic positions.

✨Exciting news: the main story of my PhD is out in Science!

Together with Christine Moene @cmoene.bsky.social, we explored what happens when you scramble the genome—revealing how Sox2’s position shapes enhancer activation.

📖 Read the full story here: www.science.org/doi/10.1126/...