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Transcriptional Regulation of Osteoblast and Chondrocyte Differentiation: Temporal Loading of Homeodomain Proteins on Chromatin of the Runx2 Gene

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Runx2, a transcription factor essential for osteoblast maturation, is also expressed in embryonic pre-cartilaginous mesenchymal condensations. However, regulatory controls for expression of Runx2 during skeletal formation are unknown. We hypothesize that Runx2 is regulated by both activators and repressors during the transition from mesenchyme to cartilage and bone. Our results demonstrate that Runx2 is a transcriptional target of Nkx3.2, a homeodomain regulatory factor for chondrogenesis. Runx2 repression by Nkx3.2 is necessary for activation of a chondrocyte-specific program of gene expression. Gene regulation in relation to several Homeodomain (HD) proteins during chondrocyte/osteoblast differentiation using Chromatin Immunoprecipitation assays was characterized in these studies. We find that multiple HD proteins constitute a regulatory network that mediates development through sequential association of HD proteins with promoter regulatory elements.

  • This report represents the work of one or more WPI undergraduate students submitted to the faculty as evidence of completion of a degree requirement. WPI routinely publishes these reports on its website without editorial or peer review.
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  • E-project-042705-224829
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  • 2005
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  • 2005-04-27
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