RRC ID 1307
Author Kou I, Ikegawa S.
Title SOX9-dependent and -independent transcriptional regulation of human cartilage link protein.
Journal J Biol Chem
Abstract Cartilage link protein is a key component of the cartilage extracellular matrix. The transcriptional regulation of the gene encoding cartilage link protein (CRTL1) is largely unknown, however. Here, we investigated the regulation of CRTL1 by SOX9, a key regulator of cartilage matrix genes and chondrogenesis. Knockdown of SOX9 resulted in decreased CRTL1 expression. SOX9 induced CRTL1 expression effectively in human non-chondrocytic immortalized cell lines as well as in mesenchymal stem cell and adult dermal fibroblast. These results indicate that, like other cartilage matrix genes, SOX9 is a key regulator of CRTL1. Unlike other cartilage matrix genes, however, the activation of CRTL1 by SOX9 and its known transcriptional co-activators L-SOX5 and SOX6 was cell type-dependent. Two cis-acting enhancer elements resided in the 5'-untranslated region of CRTL1. One contained a heptameric SOX binding sequence and showed SOX9-dependent enhancer activity in several cell lines. The other showed cell type-specific SOX9-independent enhancer activity. These findings suggest that the enhancer elements may mediate differential expression of CRTL1 during chondrocyte differentiation and maturation.
Volume 279(49)
Pages 50942-8
Published 2004-12-3
DOI 10.1074/jbc.M406786200
PII S0021-9258(20)69379-6
PMID 15456769
MeSH 5' Untranslated Regions Adenoviridae / genetics Amino Acid Motifs Base Sequence Cartilage / metabolism Cell Differentiation Cell Line Chondrocytes / cytology Chondrocytes / metabolism DNA-Binding Proteins / metabolism Enhancer Elements, Genetic Extracellular Matrix Proteins / biosynthesis* Extracellular Matrix Proteins / genetics* Fibroblasts / metabolism HeLa Cells High Mobility Group Proteins / metabolism High Mobility Group Proteins / physiology* Humans Luciferases / metabolism Mesoderm / cytology Molecular Sequence Data Nuclear Proteins / metabolism Plasmids / metabolism Protein Binding Protein Structure, Tertiary Proteoglycans / biosynthesis* Proteoglycans / genetics* RNA Interference Reverse Transcriptase Polymerase Chain Reaction SOX9 Transcription Factor SOXD Transcription Factors Skin / metabolism Stem Cells / cytology Time Factors Transcription Factors / metabolism Transcription Factors / physiology* Transcription, Genetic* Transfection
IF 4.238
Times Cited 78
Human and Animal Cells HuH-7(RCB1366)