Egr-1 Mediates Transcriptional Repression of COL2A1 Promoter Activity by Interleukin-1 beta
Following induction and activation of the early growth response (Egr)-1 transcription factor in human chondrocytes, interleukin-1 beta (IL-1 beta ) suppresses the expression of the type II collagen gene (COL2A1), associated with induction of Egr-1 binding activity in nuclear extracts. The COL2A1 pro...
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Published in | The Journal of biological chemistry Vol. 278; no. 20; pp. 17688 - 17700 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
16.05.2003
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Online Access | Get full text |
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Summary: | Following induction and activation of the early growth response (Egr)-1 transcription factor in human chondrocytes, interleukin-1 beta (IL-1 beta ) suppresses the expression of the type II collagen gene (COL2A1), associated with induction of Egr-1 binding activity in nuclear extracts. The COL2A1 proximal promoter contains overlapping binding sites for Egr-1 and Sp1 family members at -119/-112 bp and -81/-74 bp. Mutations that block binding of Sp1 and Sp3 to either site markedly reduce constitutive expression of the core promoter. IL-1 beta -induced Egr-1 binds strongly to the -119/-112 bp site, and mutations that block Egr-1 binding prevent inhibition by IL-1 beta . Cotransfection with pCMV-Egr1 potentiates the inhibition of COL2A1 promoter activity by IL-1 beta , whereas overexpression of dominant-negative Egr-1 mutant, Wilm's tumor-1 (WT1)/Egr1, Sp1, or Sp3 reverses the inhibition by IL-1 beta . Cotransfection of pGL2-COL2/Gal4, in which we substituted the critical residue for Egr-1 binding with a Gal4 binding domain and a pCMV-Gal4-Egr1 chimera permits an inhibitory response to IL-1 beta that is reversed by overexpression of Gal4-CBP. Our results indicate that IL-1 beta -induced activation of Egr-1 binding is required for inhibition of COL2A1 proximal promoter activity and suggest that Egr-1 acts as a repressor of a constitutively expressed collagen gene by preventing interactions between Sp1 and the general transcriptional machinery. |
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Bibliography: | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 |
ISSN: | 0021-9258 |
DOI: | 10.1074/jbc.M301676200 |