title: 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.
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 dose-dependent 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.
authors.affiliation: Institute of Biochemistry, Biological Research Center of the Hungarian Academy of Sciences, Szeged, Hungary.
authors.forename: Andrea
authors.initials: A
authors.lastname: Nagy
authors.forename: Erzsébet
authors.initials: E
authors.lastname: Kénesi
authors.forename: Otgonchimeg
authors.initials: O
authors.lastname: Rentsendorj
authors.forename: Annamária
authors.initials: A
authors.lastname: Molnár
authors.forename: Tibor
authors.initials: T
authors.lastname: Szénási
authors.forename: Ildikó
authors.initials: I
authors.lastname: Sinkó
authors.forename: Agnes
authors.initials: A
authors.lastname: Zvara
authors.forename: Sajit Thottathil
authors.initials: ST
authors.lastname: Oommen
authors.forename: Endre
authors.initials: E
authors.lastname: Barta
authors.forename: László G
authors.initials: LG
authors.lastname: Puskás
authors.forename: Veronique
authors.initials: V
authors.lastname: Lefebvre
authors.forename: Ibolya
authors.initials: I
authors.lastname: Kiss
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D019556:COS Cells; D002478:Cells, Cultured; D002642:Chick Embryo; D002522:Chlorocebus aethiops; D019902:Chondrocytes / Q000378:metabolism; D020219:Chondrogenesis / Q000235:genetics / Q000502:physiology; D017124:Conserved Sequence; D004247:DNA / Q000235:genetics / Q000378:metabolism; D004742:Enhancer Elements, Genetic; D019143:Evolution, Molecular; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D006023:Glycoproteins / Q000235:genetics*; D006132:Growth Plate / Q000196:embryology* / Q000378:metabolism*; D064235:Matrilin Proteins; D008969:Molecular Sequence Data; D009154:Mutation; D051839:NFI Transcription Factors / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D055758:SOX9 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D055755:SOXD Transcription Factors / Q000235:genetics / Q000378:metabolism*; D012689:Sequence Homology, Nucleic Acid; D016385:TATA Box
chemical_list: D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; D064235:Matrilin Proteins; D051839:NFI Transcription Factors; D012333:RNA, Messenger; D055758:SOX9 Transcription Factor; D055755:SOXD Transcription Factors; D004247:DNA