Thursday, March 25, 2010


Chd4 and associated proteins function as corepressors of Sox9 expression during BMP-2-induced chondrogenesis.

"Mouse embryonic fibroblasts (MEFs) differentiate into fully functional chondrocytes in response to bone morphogenetic protein-2 (BMP-2).  We 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. Let-7a targets the 3'UTR of Chd4 to promote chondrogenesis of MEFs. BMP-2 induced the upregulation of let-7a, targeting Chd4 and positively controlling the chondrogenic differentiation of MEFs."

"miR-199* might affect its target gene, Smad1, to regulate early chondrogenic differentiation"

"In hematopoietic stem cells, SNF2-like ATPase Mi-2beta is required for maintenance of multilineage differentiation in the early hematopoietic hierarchy"

"[Chd4 interacts with] Hdac1 and Hdac2 [which bind] to the promoter of Sox9 in vivo"

"BMP-2 induces the upregulation of let-7a, followed by the degradation of its target gene Chd4 and the separation of Hdac1/2 with Chd4. Subsequently, the competitive complex NF-Y-p-300 increasingly binds with the core promoter of Sox9, resulting in an open access for other positive transcription regulators of Sox9"

So inhibiting Chd4 may help in inducing chondrogenic differentiation.

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