Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 20, Issue 24, Pages -Publisher
MDPI
DOI: 10.3390/ijms20246324
Keywords
gene regulatory networks; next-generation sequencers; chondrogenesis; Sox9
Funding
- Japan Society for the Promotion of Science (JSPS) [23689079, 26713054, 17H04403, 17H05106, 18K19636]
- Rising Star Award from the American Society for Bone and Mineral Research
- Mochida Memorial Foundation Research Grant
- Naito Grant for the Advancement of Natural Science
- Grants-in-Aid for Scientific Research [26713054, 17H04403, 23689079, 17H05106, 18K19636] Funding Source: KAKEN
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Chondrogenesis is a key developmental process that molds the framework of our body and generates the skeletal tissues by coupling with osteogenesis. The developmental processes are well-coordinated by spatiotemporal gene expressions, which are hardwired with gene regulatory elements. Those elements exist as thousands of modules of DNA sequences on the genome. Transcription factors function as key regulatory proteins by binding to regulatory elements and recruiting cofactors. Over the past 30 years, extensive attempts have been made to identify gene regulatory mechanisms in chondrogenesis, mainly through biochemical approaches and genetics. More recently, newly developed next-generation sequencers (NGS) have identified thousands of gene regulatory elements on a genome scale, and provided novel insights into the multiple layers of gene regulatory mechanisms, including the modes of actions of transcription factors, post-translational histone modifications, chromatin accessibility, the concept of pioneer factors, and three-dimensional chromatin architecture. In this review, we summarize the studies that have improved our understanding of the gene regulatory mechanisms in chondrogenesis, from the historical studies to the more recent works using NGS. Finally, we consider the future perspectives, including efforts to improve our understanding of the gene regulatory landscape in chondrogenesis and potential applications to the treatment of chondrocyte-related diseases.
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