L-Sox5 and Sox6 proteins enhance chondrogenic miR-140 MicroRNA expression by strengthening dimeric Sox9 activity

Satoshi Yamashita, Shigeru Miyaki, Yoshio Kato, Shigetoshi Yokoyama, Tempei Sato, Francisco Barrionuevo, Haruhiko Akiyama, Gerd Scherer, Shuji Takada, Hiroshi Asahara

Research output: Contribution to journalArticlepeer-review

75 Scopus citations

Abstract

Sox9 plays a critical role in early chondrocyte initiation and promotion as well as repression of later maturation. Fellow Sox family members L-Sox5 and Sox6 also function as regulators of cartilage development by boosting Sox9 activation of chondrocyte- specific genes such as Col2a1 and Agc1; however, the regulatory mechanism and other target genes are largely unknown. MicroRNAs are a class of short, non-coding RNAs that act as negative regulators of gene expression by promoting target mRNA degradation and/or repressing translation. Analysis of genetically modified mice identified miR-140 as a cartilage-specific microRNA that could be a critical regulator of cartilage development and homeostasis. Recent findings suggest Sox9 promotes miR-140 expression, although the detailed mechanisms are not fully understood. In this study we demonstrate that the proximal upstream region of pri-miR-140 has chondrogenic promoter activity in vivo. We found an L-Sox5/ Sox6/Sox9 (Sox trio) response element and detailed binding site in the promoter region. Furthermore, detailed analysis suggests the DNA binding and/or transactivation ability of Sox9 as a homodimer is boosted by L-Sox5 and Sox6. These findings provide new insight into cartilage-specific gene regulation by the Sox trio.

Original languageEnglish (US)
Pages (from-to)22206-22215
Number of pages10
JournalJournal of Biological Chemistry
Volume287
Issue number26
DOIs
StatePublished - Jun 22 2012

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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