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L-Sox5 and Sox6 Proteins Enhance Chondrogenic miR-140 MicroRNA Expression by Strengthening Dimeric Sox9 Activity*
- Publication Year :
- 2012
- Publisher :
- American Society for Biochemistry and Molecular Biology, 2012.
-
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.
- Subjects :
- Transcriptional Activation
endocrine system
Chromatin Immunoprecipitation
Response element
Cartilage metabolism
Biology
Biochemistry
Polymerase Chain Reaction
Transactivation
Mice
Chondrocytes
microRNA
Gene expression
Animals
Humans
Protein Isoforms
Gene Regulation
Transgenes
Molecular Biology
Transcription factor
Regulation of gene expression
Genetics
Mice, Knockout
High Mobility Group Proteins
Promoter
SOX9 Transcription Factor
Cell Biology
Cell biology
MicroRNAs
Cartilage
HEK293 Cells
Gene Expression Regulation
embryonic structures
Dimerization
SOXD Transcription Factors
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....81e03e9eb535e7a2a7ac8eaed44c21a7