期刊
STEM CELLS
卷 32, 期 10, 页码 2780-2793出版社
WILEY
DOI: 10.1002/stem.1759
关键词
Mesenchymal stem cells; Differentiation; Osteogenesis; Epigenomics; RUNX2; Transcription factors
资金
- The Research Council of Norway through Stem Cell Research Program
- Research Council of Norway [193056]
- Norwegian Cancer Society [PR-2007-0163]
- University of Oslo
- Defence Against Cancer (Forsvar mot kreft)
- Support group for children with cancer (Stotteforeningen for kreftsyke barn)
Differentiation of osteoblasts from mesenchymal stem cells (MSCs) is an integral part of bone development and homeostasis, and may when improperly regulated cause disease such as bone cancer or osteoporosis. Using unbiased high-throughput methods we here characterize the landscape of global changes in gene expression, histone modifications, and DNA methylation upon differentiation of human MSCs to the osteogenic lineage. Furthermore, we provide a first genome-wide characterization of DNA binding sites of the bone master regulatory transcription factor Runt-related transcription factor 2 (RUNX2) in human osteoblasts, revealing target genes associated with regulation of proliferation, migration, apoptosis, and with a significant overlap with p53 regulated genes. These findings expand on emerging evidence of a role for RUNX2 in cancer, including bone metastases, and the p53 regulatory network. We further demonstrate that RUNX2 binds to distant regulatory elements, promoters, and with high frequency to gene 30 ends. Finally, we identify TEAD2 and GTF2I as novel regulators of osteogenesis.
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