Chd4 and associated proteins function as corepressors of Sox9 expression during BMP‐2–induced chondrogenesis |
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| Authors: | Wenhao Weng Yue Zhang Yongchun Yu An Hong Yuhua Ji Qiuhui Pan PhD |
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| Affiliation: | 1. Department of Clinical Laboratory Medicine, Tenth People's Hospital of Tongji University, , Shanghai, China;2. The Central Laboratory, Tenth People's Hospital of Tongji University, , Shanghai, China;3. Institute of Biology Engineering, Key Laboratory of Ministry of Education for Genetic Engineering, College of Life Science and Technology, Jinan University, , Guangzhou City, Guangdong Province, China;4. Key Laboratory of Neuroregeneration, Nantong University, , Nantong City, Jiangsu Province, China;5. Institute of Tissue Transplantation and Immunology, College of Life Science and Technology, Jinan University, , Guangzhou City, Guangdong Province, China |
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| Abstract: | Mouse embryonic fibroblasts (MEFs) differentiate into fully functional chondrocytes in response to bone morphogenetic protein‐2 (BMP‐2). However, the comprehensive proteomic aspect of BMP‐2–induced chondrogenesis remains unknown. We took advantage of quantitative proteomic analysis based on isobaric tag for relative and absolute quantitation (iTRAQ) and on‐line 2D nano‐liquid chromatography/tandem mass spectrometry (LC/MS/MS) to identify proteins differentially expressed during BMP‐2–induced chondrogenic differentiation of MEFs. We found 85 downregulated proteins, and ingenuity pathways analysis (IPA) revealed a protein‐protein network with chromodomain‐helicase‐DNA‐binding protein 4 (Chd4) in the center. Chromatin immunoprecipitation (ChIP) and nuclease hypersensitivity assays showed that Chd4, interacting with Hdac1/2, cooperates with its related proteins Kap1 and Cbx1 to bind at ?207/?148 of the Sox9 promoter. We also provided evidence that let‐7a targets the 3'UTR of Chd4 to promote chondrogenesis of MEFs. Together, our findings indicate that BMP‐2 induced the upregulation of let‐7a, targeting Chd4 and positively controlling the chondrogenic differentiation of MEFs. These findings illustrate epigenetic regulation of the chondrogenic differentiation process and also expand the understanding of the involved intracellular mechanisms. |
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| Keywords: | Chd4 Sox9 let‐7a CHONDROGENESIS BMP‐2 |
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