{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T08:30:47Z","timestamp":1786609847721,"version":"build-2736575974"},"reference-count":37,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T00:00:00Z","timestamp":1786579200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Ultraconserved elements (UCEs) are among the most evolutionarily conserved DNA sequences in vertebrate genomes, yet the biological mechanisms underlying their extraordinary conservation remain poorly understood. Using the recently developed dedUCE database comprising 12,813 human UCEs, we performed a comprehensive genome-wide analysis of their distribution relative to protein-coding genes, transcription factor (TF) genes, and long noncoding RNA (lncRNA) genes. UCEs showed a highly non-random genomic organization, with approximately 40% occurring in clusters within 20 kb genomic intervals. Non-KRAB transcription factor genes exhibited a striking sevenfold enrichment of UCEs compared with random expectation, whereas KRAB zinc-finger genes displayed an approximately tenfold depletion. Beyond TFs, UCE-rich genes were predominantly involved in developmental regulation, chromatin remodeling, RNA processing, and embryonic neurogenesis, whereas similarly large UCE-poor genes primarily encoded membrane proteins, ion channels, and synaptic components required for mature neuronal function. UCEs also demonstrated strong positional bias, with approximately fourfold enrichment near the 3\u2032 ends of protein-coding genes but no comparable distribution pattern in lncRNAs. Although lncRNA genes showed only modest overall UCE enrichment, a small subset contained numerous UCEs. These findings demonstrate that UCEs preferentially associate with master developmental regulators rather than downstream neuronal effector genes, providing new insights into the functional organization and evolutionary conservation of the human genome.<\/jats:p>","DOI":"10.3390\/ijms27167214","type":"journal-article","created":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T08:06:16Z","timestamp":1786608376000},"page":"7214","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Non-Random Association of Ultraconserved Genomic Elements (UCE) with Human Genes"],"prefix":"10.3390","volume":"27","author":[{"given":"Larisa","family":"Fedorova","sequence":"first","affiliation":[{"name":"CRI Genetics LLC, Santa Monica, CA 90404, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0587-1609","authenticated-orcid":false,"given":"Yuriy L.","family":"Orlov","sequence":"additional","affiliation":[{"name":"Center of Digital Health and AI in medicine, I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), 119991 Moscow, Russia"},{"name":"Agrarian and Technological Institute, Peoples\u2019 Friendship University of Russia (RUDN University), 117198 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oleh A.","family":"Mulyar","sequence":"additional","affiliation":[{"name":"CRI Genetics LLC, Santa Monica, CA 90404, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexei","family":"Fedorov","sequence":"additional","affiliation":[{"name":"CRI Genetics LLC, Santa Monica, CA 90404, USA"},{"name":"Center of Digital Health and AI in medicine, I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1321","DOI":"10.1126\/science.1098119","article-title":"Ultraconserved elements in the human genome","volume":"304","author":"Bejerano","year":"2004","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1093\/molbev\/msm268","article-title":"Large-scale appearance of ultraconserved elements in tetrapod genomes and slowdown of the molecular clock","volume":"25","author":"Stephen","year":"2008","journal-title":"Mol. Biol. 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