Methylation in the Core-promoter Region of the Chondromodulin-I Gene Determines the Cell-specific Expression by Regulating the Binding of Transcriptional Activator Sp3.
In: Journal of Biological Chemistry, Jg. 279 (2004-07-02), Heft 27, S. 28789-28797
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Zugriff:
Transcriptional regulation of cell- and stage-specific genes is a crucial process in the development of mesenchymal tissues. Here we have investigated the regulatory mechanism of the expression of the chondromodulin-I (ChM-I) gene, one of the chondrocyte-specific genes, in osteogenic cells using osteosarcoma (OS) cells as a model. Methylation-specific sequence analyses re- vealed that the extent of methylation in the core-promoter region of the ChM-I gene was correlated inversely with the expression of the ChM-I gene in OS primary tumors and cell lines. 5-Aza-deoxycytidine treatment induced the expression of the ChM-I gene in ChM-I-negative OS cell lines, and the induction of expression was associated tightly with the demethylation of cytosine at -52 (C(-52)) in the middle of an Spl/3 binding site to which the Sp3, but not Spl, bound. The replacement of C(-52) with methyl-cytosine or thymine abrogated Sp3 binding and also the transcription activity of the genomic fragment including C(-52). The inhibition of Sp3 expression by small interfering RNA reduced the expression of the ChM-I gene in ChM-I-positive normal chondrocytes, indicating Sp3 as a physiological transcriptional activator of the ChM-I gene. These results suggest that the methylation status of the core-promoter region is one of the mechanisms to determine the cell- specific expression of the ChM-I gene through the regu- lation of the binding of Sp3. [ABSTRACT FROM AUTHOR]
Titel: |
Methylation in the Core-promoter Region of the Chondromodulin-I Gene Determines the Cell-specific Expression by Regulating the Binding of Transcriptional Activator Sp3.
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Autor/in / Beteiligte Person: | Aoyama, Tomoki ; Okamoto, Takeshi ; Nagayama, Satoshi ; Nishijo, Koichi ; Ishibe, Tatsuya ; Yasura, Ko ; Nakayama, Tomitaka ; Nakamura, Takashi ; Toguchida, Junya |
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Zeitschrift: | Journal of Biological Chemistry, Jg. 279 (2004-07-02), Heft 27, S. 28789-28797 |
Veröffentlichung: | 2004 |
Medientyp: | academicJournal |
ISSN: | 0021-9258 (print) |
DOI: | 10.1074/jbc.M401273200 |
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