Division of Clinical Biotechnology, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-Ku, Tokyo, 113-8655, Japan.
Department of Bioengineering, Graduate School of Engineering, The University of Tokyo, Tokyo, 113-8655, Japan.
Curr Osteoporos Rep. 2023 Oct;21(5):485-492. doi: 10.1007/s11914-023-00808-4. Epub 2023 Jul 12.
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.
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.
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，发挥着独特且冗余的作用，尽管 RUNX2 在骨骼发育和几种骨骼疾病中是一个主要因素。本综述旨在概述目前对不同骨骼细胞类型中 RUNX 介导的转录调控的理解。
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推定靶基因的关联。全基因组分析和生化分析的进一步研究揭示了 RUNX 介导的先驱作用以及 RUNX2 在脂-脂相分离中的参与。RUNX 介导的基因调控的多层机制的出现有助于我们更好地理解骨骼发育和疾病，这也为思考全基因组研究如何帮助开发骨骼疾病的治疗策略提供了线索。
