{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T23:46:12Z","timestamp":1784072772369,"version":"3.55.0"},"reference-count":48,"publisher":"National Academy of Sciences","issue":"15","license":[{"start":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T00:00:00Z","timestamp":1775520000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000055","name":"HHS | NIH | National Institute on Deafness and Other Communication Disorders","doi-asserted-by":"publisher","award":["RO1DC018842"],"award-info":[{"award-number":["RO1DC018842"]}],"id":[{"id":"10.13039\/100000055","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2026,4,14]]},"abstract":"<jats:p>\n                    <jats:italic toggle=\"yes\">Myo7a<\/jats:italic>\n                    , a gene mutated in Usher syndrome and nonsyndromic deafness, encodes an unconventional myosin essential for hair cell function. Our previous work revealed that cochlear hair cells express distinct\n                    <jats:italic toggle=\"yes\">Myo7a<\/jats:italic>\n                    isoforms with unique spatial and cell type\u2013specific patterns. The canonical isoform (\n                    <jats:italic toggle=\"yes\">Myo7a-C<\/jats:italic>\n                    ) and an additional isoform (\n                    <jats:italic toggle=\"yes\">Myo7a-N<\/jats:italic>\n                    ) are co-expressed in outer hair cells (OHCs) but exhibit opposing tonotopic gradients, while inner hair cells primarily express\n                    <jats:italic toggle=\"yes\">Myo7a-C<\/jats:italic>\n                    . These isoforms arise from distinct transcriptional start sites, indicating separate regulatory inputs. Here, we identify an intronic\n                    <jats:italic toggle=\"yes\">cis-<\/jats:italic>\n                    regulatory element,\n                    <jats:italic toggle=\"yes\">EnhancerA<\/jats:italic>\n                    , essential for tonotopically graded\n                    <jats:italic toggle=\"yes\">Myo7a<\/jats:italic>\n                    expression.\n                    <jats:italic toggle=\"yes\">EnhancerA<\/jats:italic>\n                    deletion reduces MYO7A protein levels in a tonotopically varied manner, disrupts hair bundle morphogenesis, alters OHC mechanotransduction, and leads to hair cell degeneration and hearing loss. We further identify SIX2, a tonotopically expressed transcription factor that may interact with\n                    <jats:italic toggle=\"yes\">EnhancerA<\/jats:italic>\n                    to regulate\n                    <jats:italic toggle=\"yes\">Myo7a-N<\/jats:italic>\n                    in OHCs. These findings define a\n                    <jats:italic toggle=\"yes\">cis\u2013trans<\/jats:italic>\n                    regulatory axis critical for isoform-specific\n                    <jats:italic toggle=\"yes\">Myo7a<\/jats:italic>\n                    expression and cochlear function.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2519742123","type":"journal-article","created":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T16:16:01Z","timestamp":1775578561000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":1,"title":["A regulatory axis for tonotopic MYO7A expression in cochlear hair cells"],"prefix":"10.1073","volume":"123","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5396-6181","authenticated-orcid":false,"given":"Sihan","family":"Li","sequence":"first","affiliation":[{"name":"Department of Neuroscience, School of Medicine, University of 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Kyungpook National University","place":["Daegu, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-9161-5793","authenticated-orcid":false,"given":"Ayathi","family":"Gogineni","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, School of Medicine, University of Virginia","place":["Charlottesville"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franklin","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, School of Medicine, University of Virginia","place":["Charlottesville"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7360-429X","authenticated-orcid":false,"given":"Chul Hoon","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, BK21 PLUS Project for Medical Science, Brain Research Institute, Yonsei University College of Medicine","place":["Seoul, Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Un-Kyung","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Biology, College of Natural Sciences, Kyungpook National University","place":["Daegu, Republic of Korea"]},{"name":"School of Life Sciences, BK21 plus KNU Kyungpook National University Creative BioResearch Group, Kyungpook National University","place":["Daegu, Republic of Korea"]},{"name":"Advanced Bio-Resource Research Center, Kyungpook National University","place":["Daegu, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2208-6779","authenticated-orcid":false,"given":"Anthony W.","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics, University of Colorado Anschutz Medical Campus","place":["Aurora"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3047-0874","authenticated-orcid":false,"given":"Jung-Bum","family":"Shin","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, School of Medicine, University of Virginia","place":["Charlottesville"]},{"name":"Department of Cell Biology, School of Medicine, University of Virginia","place":["Charlottesville"]},{"name":"Department of Membrane and Cell Physiology, School of Medicine, University of Virginia","place":["Charlottesville"]},{"name":"Department of Otolaryngology, School of Medicine, University of Virginia","place":["Charlottesville"]},{"name":"Department of Biochemistry and Molecular Genetics, School of Medicine, University of 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