Daniel Hoffmann 🌼
A single nucleotide insertion in a non-coding region (enhancer Enh13) leads to formation of testes in female mice.
https://www.nature.com/articles/s41467-026-71328-9
#genetics
A single-nucleotide enhancer mutation overrides chromosomal sex to drive XX male development - Nature Communications

A single base pair insertion in the Sox9 enhancer, Enh13, mediates XX female-to-male sex reversal. This subtle non-coding mutation reconfigures transcriptional regulation, enhances Sox9 expression, revealing Enh13 as a binary switch governing sexual fate.

Nature
Apr 10 at 1:23pmWeb
Show threadJames Hawley, PhD1d ago

@Daniel_Hoffmann I've seen lots of genetic abnormalities related to DNA methylation and mutations of the X/Y chromosomes, but I don't know if I've seen such a strong phenotypic effect from epigenetic regulation of a transcription factor via indels in an enhancer region before. The only other one that comes to mind is F-syndrome/polydactyly/brachydactyly from structural variants:

https://doi.org/10.1016/j.cell.2015.04.004

I'll have to give this a read.

Show threadIsabelle Stévant1d ago
@Daniel_Hoffmann @AnaVinuela Enh13 of the Sox9 gene is soooo puzzling 🤯 This is one of the so many reasons I love studying sex determination, we literally play with the sex switch ⚖️