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• W2144861489 abstract "The Sry-related high-mobility-group box transcription factor Sox9 recruits the redundant L-Sox5 and Sox6 proteins to effect chondrogenesis, but the mode of action of the trio remains unclear. We identify here a highly conserved 359-bp sequence 10 kb upstream of the Agc1 gene for aggrecan, a most essential cartilage proteoglycan and key marker of chondrocyte differentiation. This sequence directs expression of a minimal promoter in both embryonic and adult cartilage in transgenic mice, in a manner that matches Agc1 expression. The chondrogenic trio is required and sufficient to mediate the activity of this enhancer. It acts directly, Sox9 binding to a critical cis-acting element and L-Sox5/Sox6 binding to three additional elements, which are cooperatively needed. Upon binding to their specific sites, L-Sox5/Sox6 increases the efficiency of Sox9 binding to its own recognition site and thereby robustly potentiates the ability of Sox9 to activate the enhancer. L-Sox5/Sox6 similarly secures Sox9 binding to Col2a1 (encoding collagen-2) and other cartilage-specific enhancers. This study thus uncovers critical cis-acting elements and transcription factors driving Agc1 expression in cartilage and increases understanding of the mode of action of the chondrogenic Sox trio." @default.
• W2144861489 created "2016-06-24" @default.
• W2144861489 creator A5015694516 @default.
• W2144861489 creator A5077076733 @default.
• W2144861489 date "2008-08-01" @default.
• W2144861489 modified "2023-10-10" @default.
• W2144861489 title "L-Sox5 and Sox6 Drive Expression of the Aggrecan Gene in Cartilage by Securing Binding of Sox9 to a Far-Upstream Enhancer" @default.
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• W2144861489 doi "https://doi.org/10.1128/mcb.00695-08" @default.
• W2144861489 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2519711" @default.
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• W2144861489 hasPublicationYear "2008" @default.
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