[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].
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.
Abramova
M V
MV
Institute of Cytology, Russian Academy of Sciences, St. Petersburg, 194064 Russia.
Kukushkin
A N
AN
Pospelova
T V
TV
Svetlikova
S B
SB
Pospelov
V A
VA
D017500:Adenovirus E1A Proteins / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D002843:Chromatin / Q000648:ultrastructure*; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects; D005786:Gene Expression Regulation; D016762:Genes, fos; D011905:Genes, ras; D056572:Histone Deacetylase Inhibitors; D006657:Histones / Q000378:metabolism; D009154:Mutation; D009687:Nuclear Proteins / Q000378:metabolism; D019319:Okadaic Acid / Q000494:pharmacology; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors; D010766:Phosphorylation / Q000187:drug effects; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051381:Rats; D027602:Serum Response Element; D026362:Serum Response Factor / Q000235:genetics / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors; D014158:Transcription, Genetic; D050807:ets-Domain Protein Elk-1
D017500:Adenovirus E1A Proteins; D002843:Chromatin; D004268:DNA-Binding Proteins; C494114:Elk1 protein, rat; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D026362:Serum Response Factor; D015534:Trans-Activators; D014157:Transcription Factors; D050807:ets-Domain Protein Elk-1; D019319:Okadaic Acid; D010749:Phosphoprotein Phosphatases