Mapping of chromatin architecture and enhancer-promoter interactions in the cochlea.

Introduction: Chromatin interactions, particularly those between promoters and distal enhancers, enable precise gene regulation in specialized tissues, like the cochlea in the inner ear. Disruptions in these long-range interactions between enhancers and gene promoters are linked to hereditary hearing loss. For many genes important to cochlear development and function, the distal regulatory elements that control their expression remain unknown. Identifying these elements and studying their regulatory roles is challenging due to their distance from target genes and the spatial complexity of chromatin architecture. Methods: To address this, we employed Micro-C, a high-resolution chromatin conformation capture technique for mapping chromatin interactions, to construct a cochlea-specific chromatin interaction map. We then integrated epigenomic and transcriptomic data to interpret enhancer-promoter interactions involved in gene regulation. Results: Our analysis revealed unbiased tissue-specific long-range interactions, and some of those interactions overlapped with disease-associated deletions and active regulatory elements, such as the Discussion: This study establishes a high-resolution interaction map of the cochlea, demonstrating how non-coding variants can impair tissue-specific gene regulation in hearing loss. Our dataset provides a foundational resource for analyzing hereditary hearing loss mutations and investigating transcriptional regulation in the cochlea.