GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE329nnn/GSE329998/primaryOK200GenomicsHomo sapiensGenome binding/occupancy profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE329998GEOGSEfalseDistal Enhancer-Insulator Module of GDF6 is Essential for Cochlear Formation [ATAC-seq]Inner-ear malformations cause congenital hearing loss, and several genes are known to guide inner-ear development. However, the contribution of noncoding regulatory elements remains largely unclear. This study investigates the function of distal enhancer elements in the transcriptional regulation of GDF6, a gene crucial for cochlear development. Using mouse models with targeted deletions, human iPSC-derived ear organoids (IEO), and CRISPR interference (CRISPRi) techniques, we identified a downstream regulatory interval harboring a developmental enhancer required to maintain GDF6 expression during otic epithelial maturation, vital for cochlear morphogenesis. Deletion of this regulatory region or targeting of CRISPRi-based repressors to these regions resulted in decreased GDF6 expression, failure of otic-epithelium development, and prevention of hair cell-like differentiation, reflecting cochlear aplasia observed in patients with corresponding genomic deletions. These findings highlight the essential role of long-range regulatory elements in auditory development and illustrate how their disruption contributes to human deafness.2026/06/05GSE329998GSM9714909GSM971490824676329998Homo sapiens[42313493]