Evolutionarily conserved, growth plate zone-specific regulation of the matrilin-1 promoter: L-Sox5/Sox6 and Nfi factors bound near TATA finely tune activation by Sox9

Andrea Nagy, Erzsébet Kénesi, Otgonchimeg Rentsendorj, Annamária Molnár, Tibor Szénási, Ildikó Sinkó, A. Zvara, Sajit Thottathil Oommen, E. Barta, L. Puskás, Veronique Lefebvre, I. Kiss

Research output: Article

23 Citations (Scopus)

Abstract

To help uncover the mechanisms underlying the staggered expression of cartilage-specific genes in the growth plate, we dissected the transcriptional mechanisms driving expression of the matrilin-1 gene (Matn1). We show that a unique assembly of evolutionarily conserved cis-acting elements in the Matn1 proximal promoter restricts expression to the proliferative and prehypertrophic zones of the growth plate. These elements functionally interact with distal elements and likewise are capable of restricting the domain of activity of a pancartilaginous Col2a1 enhancer. The proximal elements include a Pe1 element binding the chondrogenic L-Sox5, Sox6, and Sox9 proteins, a SI element binding Nfi proteins, and an initiator Ine element binding the Sox trio and other factors. Sox9 binding to Pe1 is indispensable for functional interaction with the distal promoter. Binding of L-Sox5/Sox6 to Ine and Nfib to SI modulates Sox9 transactivation in a protein dosedependent manner, possibly to enhance Sox9 activity in early stages of chondrogenesis and repress it at later stages. Hence, our data suggest a novel model whereby Sox and Nfi proteins bind to conserved Matn1 proximal elements and functionally interact with each other to finely tune gene expression in specific zones of the cartilage growth plate.

Original languageEnglish
Pages (from-to)686-699
Number of pages14
JournalMolecular and Cellular Biology
Volume31
Issue number4
DOIs
Publication statusPublished - febr. 2011

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Matrilin Proteins
Growth Plate
Genes
Cartilage
Chondrogenesis
Proteins
Transcriptional Activation
Carrier Proteins
Gene Expression

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Evolutionarily conserved, growth plate zone-specific regulation of the matrilin-1 promoter : L-Sox5/Sox6 and Nfi factors bound near TATA finely tune activation by Sox9. / Nagy, Andrea; Kénesi, Erzsébet; Rentsendorj, Otgonchimeg; Molnár, Annamária; Szénási, Tibor; Sinkó, Ildikó; Zvara, A.; Oommen, Sajit Thottathil; Barta, E.; Puskás, L.; Lefebvre, Veronique; Kiss, I.

In: Molecular and Cellular Biology, Vol. 31, No. 4, 02.2011, p. 686-699.

Research output: Article

Nagy, Andrea ; Kénesi, Erzsébet ; Rentsendorj, Otgonchimeg ; Molnár, Annamária ; Szénási, Tibor ; Sinkó, Ildikó ; Zvara, A. ; Oommen, Sajit Thottathil ; Barta, E. ; Puskás, L. ; Lefebvre, Veronique ; Kiss, I. / Evolutionarily conserved, growth plate zone-specific regulation of the matrilin-1 promoter : L-Sox5/Sox6 and Nfi factors bound near TATA finely tune activation by Sox9. In: Molecular and Cellular Biology. 2011 ; Vol. 31, No. 4. pp. 686-699.
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