在这个TAD中，课题组发现了代谢反应的遗传回路和与冬眠相关的顺式元件与邻近基因形成调控联系。小鼠中单个顺式元件的缺失会不同地改变Fto、Irx3和Irx5的表达，重塑下游基因表达程序，并以不同的方式影响代谢、睡眠、肥胖发生和觅食。他们的发现显示了冬眠动物的趋同进化如何精确定位代谢控制的功能遗传机制，在单个CREs中编码多种效应。
据悉，顺式调控元件（CREs）驱动表型多样性，但CREs如何与功能联系在一起仍不清楚。他们的研究阐明了与哺乳动物冬眠和代谢灵活性进化相关的保守顺式元件的功能。基因组分析显示，冬眠动物的拓扑相关结构域（TADs）富集于收敛性变化，包括脂肪质量和肥胖（Fto）位点。
附：英文原文
Title: Conserved noncoding cis elements associated with hibernation modulate metabolic and behavioral adaptations in mice
Author: Susan Steinwand, Cornelia Stacher Hrndli, Elliott Ferris, Jared Emery, Josue D. Gonzalez Murcia, Adriana Cristina Rodriguez, Riley J. Spotswood, Amandine Chaix, Alun Thomas, Crystal Davey, Christopher Gregg
Issue&Volume: 2025-07-31
Abstract: Cis-regulatory elements (CREs) drive phenotypic diversity, yet how CREs are causally linked to function remains largely unclear. Our study elucidates functions for conserved cis elements associated with the evolution of mammalian hibernation and metabolic flexibility. Genomic analyses revealed topologically associated domains (TADs) enriched for convergent changes in hibernators, including the Fat Mass & Obesity (Fto) locus. In this TAD, we uncovered genetic circuits for metabolic responses and hibernation-linked cis elements forming regulatory contacts with neighboring genes. Deletions of individual cis elements in mice differentially altered Fto, Irx3, and Irx5 expression, reshaping downstream gene expression programs and affecting metabolism, torpor, obesogenesis, and foraging in distinct ways. Our findings show how convergent evolution in hibernators pinpoints functional genetic mechanisms of metabolic control, with multiple effects encoded in single CREs.
DOI: adp4701
Source: https://www.science.org/doi/10.1126/science.adp4701