Expression, methylation and chromatin structure of the p53 gene in untransformed and human T-cell leukemia virus type I-transformed human T-lymphocytes.
p53 is a nuclear protein associated with cellular transformation and normal cellular proliferation. Some transformed cells have been found to have one or several quantitative or qualitative abnormalities of p53. We studied expression, kinetics, phosphorylation, DNA methylation and chromatin structure of p53 in resting and proliferating untransformed T-lymphocytes and in human T-cell leukemia virus type I transformed T-lymphocytes from the same individuals. p53 expression is indistinguishable in transformed compared to untransformed proliferating T-lymphocytes by: (1) p53 mRNA levels, (2) rate of synthesis and stability of p53 protein, (3) change in protein stability after exposure to an inhibitor of protein synthesis, (4) presence of phosphorylation of the p53 protein. Resting T-lymphocytes from these same individuals did not express p53. No difference in DNA methylation and chromatin structure of the p53 gene was observed in either resting or proliferating untransformed, or virally transformed T-lymphocytes. The gene was fully methylated and resistant to DNAase I over its entire coding region but was demethylated and contained DNAase I hypersensitive sites in a distinct region 5' of the site of initiation of transcription.
Lübbert
M
M
UCLA Department of Medicine, Division of Hematology/Oncology 90024.
Miller
C W
CW
Kahan
J
J
Koeffler
H P
HP
D002460:Cell Line; D002472:Cell Transformation, Viral; D002843:Chromatin / Q000648:ultrastructure*; D003850:Deoxyribonuclease I; D005786:Gene Expression Regulation; D015368:Human T-lymphotropic virus 1; D006801:Humans; D015151:Immunoblotting; D008745:Methylation; D009363:Neoplasm Proteins / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D010750:Phosphoproteins / Q000235:genetics*; D013601:T-Lymphocytes / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53
D002843:Chromatin; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D010750:Phosphoproteins; D016159:Tumor Suppressor Protein p53; D003850:Deoxyribonuclease I