染色质三维结构与基因调控网络在儿童代谢性疾病中的遗传学机制进展

Progress in genetic mechanisms of chromatin 3D structure and gene regulatory networks in pediatric metabolic disorders

摘要

基因表达不仅由编码序列决定,还受非编码区调控元件的调控。作为关键表观遗传因素,染色质三维结构的动态变化与疾病发生密切相关。三维基因组通过空间构象将远距离的启动子、增强子等顺式调控元件聚集,从而调控胰岛素分泌、脂肪细胞分化及能量代谢等关键通路中的基因表达。本文综述了染色质三维结构的基本特征及其在儿童代谢性疾病中的研究进展,重点探讨其在肥胖、糖尿病和非酒精性脂肪肝等疾病中的调控机制。通过了解染色质三维结构变化和基因调控之间的关系,从而更深入理解儿童代谢性疾病。

Abstract

Gene expression is not solely determined by coding sequences but is also regulated by non-coding cis-regulatory elements.As a key epigenetic factor, the dynamic organization of chromatin in three-dimensional (3D) space plays a critical role in the onset and progression of disease.The 3D genome architecture enables distal cis-regulatory elements, such as promoters and enhancers, to be spatially juxtaposed, thereby orchestrating gene expression in essential metabolic pathways, including insulin secretion, adipocyte differentiation, and energy metabolism.This review summarizes the fundamental characteristics of chromatin 3D structure and highlights recent advances in its role in pediatric metabolic diseases.Particular attention is given to its regulatory mechanisms in obesity, diabetes, and nonalcoholic fatty liver disease.Understanding the interplay between 3D genome organization and gene regulation provides novel insights into the molecular basis of pediatric metabolic diseases.

关键词

染色质三维结构 / 三维基因组 / 基因表达调控 / 儿童代谢性疾病 / Hi-C技术

Key words

chromatin 3D structure / three-dimensional genomics / gene expression regulation / pediatric metabolic diseases / Hi-C

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基金资助

国家重点研发计划(2021YFC2701900, 2021YFC2701903);上海交通大学医学院上海同仁医院科研基金(TRYJ2024LC03);国家自然科学基金(82100915)