Ultraconserved Elements Mark Genes Involved in Multilayered Regulation and Human Development
- 1CRI Genetics LLC, Santa Monica, CA 90404, USA
- 2Center 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
- 3Peoples’ Friendship University of Russia (RUDN University), 117198 Moscow, Russia
Abstract
Ultraconserved elements (UCEs) are genomic sequences exhibiting exceptional evolutionary conservation across vertebrate taxa, yet their biological functions remain poorly understood. Here, we investigated the functional and expression characteristics of human protein-coding genes containing UCEs. Observed UCE distributions across Gene Ontology and manually curated, mutually exclusive functional groups of genes were compared with 1000 randomized UCE datasets that preserved natural UCE clustering. UCEs are preferentially located within genes involved in multilayered regulation, including transcription, chromatin organization, RNA processing, and ubiquitin-mediated protein regulation, whereas genes associated with membrane, extracellular, structural, transport, and metabolic functions are relatively UCE-poor. Within enriched groups, UCE accumulation is concentrated in multifunctional developmental regulators rather than in constitutive cellular machinery. Compared with length-matched UCE-free controls, UCE-rich genes showed higher and broader expression across 68 adult tissues and significantly higher prenatal expression in all seven organs examined. This expression excess was greatest in the developing brain and cerebellum and was most pronounced during early prenatal development. UCE-rich transcription factors are specifically enriched in developmental and chromatin-regulatory programs, including HOX-related embryonic patterning. These findings indicate that UCEs preferentially mark genes involved in several levels of cellular regulation and link ultraconservation to multilayered gene regulation and early human development.
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BibTeX
@article{fedorova2026ultraconserved,
title = {{Ultraconserved Elements Mark Genes Involved in Multilayered Regulation and Human Development}},
author = {Larisa Fedorova and Georgiy S. Lebedev and Yuriy L. Orlov and Oleh A. Mulyar and Alexei Fedorov},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = nov,
doi = {10.3390/ijms27219981},
url = {https://www.mdpi.com/1422-0067/27/21/9981},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Ultraconserved Elements Mark Genes Involved in Multilayered Regulation and Human Development
AU - Larisa Fedorova
AU - Georgiy S. Lebedev
AU - Yuriy L. Orlov
AU - Oleh A. Mulyar
AU - Alexei Fedorov
PY - 2026
DA - 2026/11/07
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27219981
UR - https://www.mdpi.com/1422-0067/27/21/9981
AB - Ultraconserved elements (UCEs) are genomic sequences exhibiting exceptional evolutionary conservation across vertebrate taxa, yet their biological functions remain poorly understood. Here, we investigated the functional and expression characteristics of human protein-coding genes containing UCEs. Observed UCE distributions across Gene Ontology and manually curated, mutually exclusive functional groups of genes were compared with 1000 randomized UCE datasets that preserved natural UCE clustering. UCEs are preferentially located within genes involved in multilayered regulation, including transcription, chromatin organization, RNA processing, and ubiquitin-mediated protein regulation, whereas genes associated with membrane, extracellular, structural, transport, and metabolic functions are relatively UCE-poor. Within enriched groups, UCE accumulation is concentrated in multifunctional developmental regulators rather than in constitutive cellular machinery. Compared with length-matched UCE-free controls, UCE-rich genes showed higher and broader expression across 68 adult tissues and significantly higher prenatal expression in all seven organs examined. This expression excess was greatest in the developing brain and cerebellum and was most pronounced during early prenatal development. UCE-rich transcription factors are specifically enriched in developmental and chromatin-regulatory programs, including HOX-related embryonic patterning. These findings indicate that UCEs preferentially mark genes involved in several levels of cellular regulation and link ultraconservation to multilayered gene regulation and early human development.
SN - 1422-0067
ER -