Chromatin relaxation by overexpression of mutant p53, HPV16-E6, or cyclin G transgenes.
In this study, using a cell line that carries endogenous wild-type p53 genes, we show that transfection of cells with mutant p53, HPV16-E6, or cyclin G transgenes results in the disruption of higher-order chromatin structure, as evidenced by enhanced sensitivity to micrococcal nuclease. Multiple mechanisms may contribute to this phenotype, including histone H1 phosphorylation, direct binding of oncoproteins to nuclear matrix attachment sites, and altered expression of component genes of the p53 pathway, whose products may function in maintenance of chromatin structure.
Division of Basic Science, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. smithml@box-s.nih.gov
M L
ML
Smith
R A
RA
Bortnick
M S
MS
Sheikh
A J
AJ
Fornace
D002277:Carcinoma; D002843:Chromatin; D003106:Colon; D056746:Cyclin G; D056766:Cyclin G1; D016213:Cyclins / Q000235:genetics*; D015870:Gene Expression; D005814:Genes, Viral / Q000502:physiology; D016158:Genes, p53 / Q000235:genetics / Q000502:physiology*; D006657:Histones / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008836:Micrococcal Nuclease; D009154:Mutation; D009687:Nuclear Proteins; D009707:Nucleosomes; D009856:Oncogene Proteins, Viral / Q000235:genetics*; D010766:Phosphorylation; D011506:Proteins / Q000032:analysis; D011518:Proto-Oncogene Proteins / Q000032:analysis; D051736:Proto-Oncogene Proteins c-mdm2; D012097:Repressor Proteins; D016160:Retinoblastoma Protein / Q000378:metabolism; D014162:Transfection; D019076:Transgenes; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000032:analysis; D015678:Viral Structural Proteins / Q000235:genetics; D000097642:GADD45 Proteins
D002843:Chromatin; D056746:Cyclin G; D056766:Cyclin G1; D016213:Cyclins; D006657:Histones; D047908:Intracellular Signaling Peptides and Proteins; D008836:Micrococcal Nuclease; D009687:Nuclear Proteins; D009707:Nucleosomes; D009856:Oncogene Proteins, Viral; D011506:Proteins; D011518:Proto-Oncogene Proteins; D051736:Proto-Oncogene Proteins c-mdm2; D012097:Repressor Proteins; D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53; D015678:Viral Structural Proteins; D000097642:GADD45 Proteins; C534702:CCNG1 protein, human; C068651:E6 protein, Human papillomavirus type 16; C497206:MDM2 protein, human