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  • Title: [Role of the TCF phosphorylation state and the chromatin structure in the negative transcription regulation of the c-fos proto-oncogene in E1A + c-Ha-ras transformed cells].
    Author: Abramova MV, Kukushkin AN, Pospelova TV, Svetlikova SB, Pospelov VA.
    Journal: Mol Biol (Mosk); 2002; 36(1):66-75. PubMed ID: 11862715.
    Abstract:
    As compared with normal rat embryo fibroblasts (REF), c-fos transcription is suppressed in REF transformed with the E1A and cHa-ras complementing oncogenes. Negative regulation of the fos promoter is due to the serum-responsive element (SRE) constantly bound with the serum response factor (SRF) and with the ternary complex factor (TCF), which form the SRF/SRF/TCF complex. Possible mechanisms of the c-fos suppression were studied, including changes in the TCF content and phosphorylation and replacement of TCF by repressor proteins. In addition, the transcription factors were tested for DNA-binding activity, and c-fos transcription was analyzed by RT-PCR in various cell culture conditions and in the presence of phosphatase and histone deacetylase inhibitors. The c-fos suppression in transformed REF was explained by formation of a transcriptionally inactive chromatin structure in the fos promoter region as a result of histone deacetylation, rather than by insufficient TCF phosphorylation.
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