TY - JOUR
T1 - Evolutionarily conserved, growth plate zone-specific regulation of the matrilin-1 promoter
T2 - L-Sox5/Sox6 and Nfi factors bound near TATA finely tune activation by Sox9
AU - Nagy, Andrea
AU - Kénesi, Erzsébet
AU - Rentsendorj, Otgonchimeg
AU - Molnár, Annamária
AU - Szénási, Tibor
AU - Sinkó, Ildikó
AU - Zvara, Ágnes
AU - Oommen, Sajit Thottathil
AU - Barta, Endre
AU - Puskás, László G.
AU - Lefebvre, Veronique
AU - Kiss, Ibolya
PY - 2011/2
Y1 - 2011/2
N2 - 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.
AB - 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.
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U2 - 10.1128/MCB.00019-10
DO - 10.1128/MCB.00019-10
M3 - Article
C2 - 21173167
AN - SCOPUS:79251553744
SN - 0270-7306
VL - 31
SP - 686
EP - 699
JO - Molecular and cellular biology
JF - Molecular and cellular biology
IS - 4
ER -