ORIGINAL RESEARCH article
Front. Mol. Biosci.
Sec. Genome Organization and Dynamics
Volume 12 - 2025 | doi: 10.3389/fmolb.2025.1683964
Mapping of Chromatin Architecture and Enhancer-Promoter Interactions in the Cochlea
Provisionally accepted
- Department of Biomedical Sciences, Creighton University, Omaha, United States
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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. 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. 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 NR2F1 locus, which is involved in Bosch-Boonstra-Schaaf optic atrophy syndrome (BBSOAS), and the DLX5/6 locus, which is linked to Split-Hand/Foot Malformation Type 1 (SHFM1), suggesting that structural variants disrupting local chromatin architecture cause transcriptional dysregulation. 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.
Keywords: 3D genome organization, Micro-C, Chromatin architecture, enhancer-promoterinteractions, Non-coding mutation, Hearing Loss
Received: 11 Aug 2025; Accepted: 23 Sep 2025.
Copyright: © 2025 Ege, Bloom, Zhou, Liu and Tao. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Litao Tao, litaotao@creighton.edu
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