Sex-determining 3D regulatory hubs revealed by genome spatial auto-correlation analysis [Hi-C]

Mammalian sex is determined by a network of antagonistic genes that are well characterized. However, its non-coding regulation is still largely unknown. Here we explore the 3D chromatin landscape of sex determination in vivo. We integrate Hi-C with ChIP-seq experiments using METALoci, a novel genome spatial auto-correlation analysis approach that identifies 3D regulatory hubs across the genome. We uncover a prominent rewiring of chromatin interactions during sex determination. By combining predictive approaches and validations in transgenic mice we identify a novel Fgf9 regulatory hub, which deletion results in male-to-female sex reversal. Hi-C experiments in FACS-sorted embryonic mouse gonadal populations.