Runt-related Transcription Factors and Gene Regulatory Mechanisms in Skeletal Development and Diseases.

IF 4.2 2区医学 Q1 ENDOCRINOLOGY & METABOLISM

Current Osteoporosis Reports Pub Date : 2023-10-01 Epub Date: 2023-07-12 DOI:10.1007/s11914-023-00808-4

Hironori Hojo, Shinsuke Ohba

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Abstract

Purpose of review: Runt-related transcription factors (RUNX) play critical roles in skeletal development, metabolism, and diseases. In mammals, three RUNX members, namely RUNX1, RUNX2, and RUNX3, play distinct and redundant roles, although RUNX2 is a dominant factor in skeletal development and several skeletal diseases. This review is to provide an overview of the current understanding of RUNX-mediated transcriptional regulation in different skeletal cell types.

Recent findings: Advances in chromatin immunoprecipitation and next-generation sequencing (ChIP-seq) have revealed genome-wide RUNX-mediated gene regulatory mechanisms, including their association with cis-regulatory elements and putative target genes. Further studies with genome-wide analysis and biochemical assays have shed light on RUNX-mediated pioneering action and involvements of RUNX2 in lipid-lipid phase separation. Emerging multi-layered mechanisms of RUNX-mediated gene regulations help us better understanding of skeletal development and diseases, which also provides clues to think how genome-wide studies can help develop therapeutic strategies for skeletal diseases.

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骨骼发育和疾病中与Runt相关的转录因子和基因调控机制。

综述目的：Runt相关转录因子（RUNX）在骨骼发育、代谢和疾病中发挥着关键作用。在哺乳动物中，三个RUNX成员，即RUNX1、RUNX2和RUNX3，发挥着不同和多余的作用，尽管RUNX2是骨骼发育和几种骨骼疾病的主导因素。这篇综述旨在概述目前对RUNX介导的不同骨骼细胞类型的转录调控的理解。最近的发现：染色质免疫沉淀和下一代测序（ChIP-seq）的进展揭示了全基因组RUNX介导的基因调控机制，包括它们与顺式调控元件和假定的靶基因的关系。通过全基因组分析和生化测定的进一步研究揭示了RUNX介导的开创性作用以及RUNX2在脂质相分离中的参与。RUNX介导的基因调控的新出现的多层机制有助于我们更好地了解骨骼发育和疾病，这也为思考全基因组研究如何帮助制定骨骼疾病的治疗策略提供了线索。

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来源期刊

Current Osteoporosis Reports Medicine-Endocrinology, Diabetes and Metabolism

CiteScore

8.80

自引率

2.30%

发文量

期刊介绍： This journal intends to provide clear, insightful, balanced contributions by international experts that review the most important, recently published clinical findings related to the diagnosis, treatment, management, and prevention of osteoporosis. We accomplish this aim by appointing international authorities to serve as Section Editors in key subject areas, such as current and future therapeutics, epidemiology and pathophysiology, and evaluation and management. Section Editors, in turn, select topics for which leading experts contribute comprehensive review articles that emphasize new developments and recently published papers of major importance, highlighted by annotated reference lists. An international Editorial Board reviews the annual table of contents, suggests articles of special interest to their country/region, and ensures that topics are current and include emerging research. Commentaries from well-known figures in the field are also provided.