Looking forward to exciting science and to connect with colleagues in Milan at the Neurogenomics conference @humantechnopole.bsky.social Presenting our research ( @svergult.bsky.social @lisahamerlinck.bsky.social ) on noncoding variants in the FOXG1 locus during the poster session (#88) #neurogen25

Finally, CRISPR-Cas9 deletion of the enhancer cluster and TAD boundary in NPCs resulted in decreased FOXG1 transcription.

As FOXG1 plays a crucial role in differentiation and proliferation of neural progenitor cells (NPCs), we performed sequential UMI-4C and CUT&RUN assays during NPC differentiation. We found dynamic activation of, and FOXG1 interaction with, our enhancer cluster.

Integrating epigenomics data, 3D chromatin interaction profiles (Hi-C, UMI-4C), and in vivo enhancer assays in zebrafish, we uncovered multiple regulatory elements within this CARR, including a neuronal enhancer cluster and a conserved boundary of the FOXG1 TAD.

We identified a de novo non-coding deletion in an individual with FOXG1 syndrome, allowing us to delineate a ~124 kb commonly affected regulatory region (CARR). Deletion of this region resulted in reduced FOXG1 expression and TAD fusion in patient cells.

📢 New preprint from the FunGen lab @svergult.bsky.social on how non-coding structural variants disrupt FOXG1 regulation during early neurodevelopment. Great teamwork from Lisa Hamerlinck and everyone in the lab! Thread below👇
www.medrxiv.org/content/10.1...

#GeneRegulation #RareDisease #Epigenomics