Document Detail


Oligonucleotide decoy mimicking alphaA-crystallin-binding protein 1 binding site on mouse Col2a1 enhancer stimulates transcription from the adjacent Col2a1 promoter in chondrogenic ATDC5 cell.
MedLine Citation:
PMID:  15456958     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
A 48-bp sequence element in intron 1 of the alpha1(II) collagen gene (Col2a1) acts as an enhancer of Col2a1 transcription and contains binding sites for the transcription activator SOX9 and repressor alphaA-crystallin-binding protein 1 (CRYBP1). We hypothesized that abrogating CRYBP1 binding should increase transcription from a promoter associated with the Col2a1 enhancer. We tested this hypothesis by cotransfecting an oligonucleotide (ODN) decoy for CRYBP1 and a luciferase-based reporter vector under the transcriptional control of the Col2a1 promoter linked to the 100-bp enhancer in chondrogenic ATDC5 cells. As a control, we used decoy ODN corresponding to the SOX9 binding site. Transfection with CRYBP1 decoy increased luciferase activity by >2.5-fold in the absence or presence of insulin, whereas SOX9 decoy ODN decreased luciferase activity to about 50% under similar conditions. In addition, the repressive effect of interleukin-1 on Col2a1 transcription through decreasing SOX9 messenger ribonucleic acid (mRNA) expression and increasing CRYBP1 mRNA expression, was counteracted by CRYBP1 decoy ODN. These results provide a rationale for gene therapy in degenerative joint diseases by elevating Col2a1 expression in chondrocytes through oligomimetics of repressor binding sites.
Authors:
Hiroshi Yamagiwa; Yoshihiko Yamada; Mark E Bolander; Gobinda Sarkar
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Molecular biotechnology     Volume:  28     ISSN:  1073-6085     ISO Abbreviation:  Mol. Biotechnol.     Publication Date:  2004 Sep 
Date Detail:
Created Date:  2004-09-30     Completed Date:  2005-04-28     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  9423533     Medline TA:  Mol Biotechnol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1-8     Citation Subset:  IM    
Affiliation:
Dept. of Orthopedic Surgery, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Base Sequence
Binding Sites / genetics
Cell Line, Tumor
Chondrocytes / metabolism*
Collagen Type II / biosynthesis,  genetics*
DNA-Binding Proteins / antagonists & inhibitors*,  metabolism
Enhancer Elements, Genetic / genetics*
High Mobility Group Proteins / genetics,  metabolism
Interleukin-1 / pharmacology
Mice
Molecular Mimicry
Molecular Sequence Data
Oligodeoxyribonucleotides / genetics*
Promoter Regions, Genetic / genetics
RNA, Messenger / analysis,  metabolism
SOX9 Transcription Factor
Transcription Factors / antagonists & inhibitors*,  genetics,  metabolism
Transcriptional Activation* / drug effects
Transfection
Chemical
Reg. No./Substance:
0/Col2a1 protein, mouse; 0/Collagen Type II; 0/DNA-Binding Proteins; 0/High Mobility Group Proteins; 0/Hivep1 protein, mouse; 0/Interleukin-1; 0/Oligodeoxyribonucleotides; 0/RNA, Messenger; 0/SOX9 Transcription Factor; 0/Sox9 protein, mouse; 0/Transcription Factors

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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