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Biomedical subjects

R Piva

Publications and source records attributed to R Piva.

At least 109 records · Page 6Linked to original sources
PubMedDate not supplied

Methylation pattern of the HLA-DR alpha gene in human tissues.

The CCGG and GCGC sites of the human HLA-DR alpha gene are hypermethylated in human tissues (including B-lymphocytes, T-lymphocytes, muscle, brain, sperm, skin, kidney, suprarenal and mammary glands) and three B-lymphoid cell lines. Therefore, the HLA-DR alpha gene can be transcribed even though extensively methylated. The only exception to the hypermethylated state of the HLA-DR alpha gene is represented by one or both of the two HhaI sites (H1 and H2) localized in the 5' portion of the gene. Analysis of the computer-generated secondary structure of the HLA-DR alpha mRNA suggests that the H1 and H2 sites belong to a region (5'-GAGCGCCCA-3'/5'-UGAGCGCUC-3') exhibiting extensive base pairing. Therefore, unmethylation of these CG sites can contribute in preventing mCG----TG/CA changes in this region, which would lead to extensive alterations of the secondary structure of the 5' portion of the HLA-DR alpha MRNA. On the other hand, the selective pressure to maintain unaltered the methylated CG dinucleotides in the coding regions of the HLA-DR alpha gene could be due to codon restrictions, since the majority of the methylation-related CG----TG or CG----CA variations would generate aminoacid changes. Accordingly, the analysis of different HLA-DR alpha genomic sequences indicates that variations of the CpG dinucleotides occur only in the non-coding portions of the HLA-DR alpha gene.

Base Sequence↗
PubMedDate not supplied

Binding of nuclear factors to the IFN-gamma consensus sequence of the human HLA-DR alpha gene: effects of IFN-gamma on tumor cell lines.

The binding of nuclear proteins from human tumor cells to synthetic double stranded oligonucleotides mimicking upstream regions of the HLA-DR alpha gene was studied. As the HLA-DR alpha gene is inducible by interferon(IFN)-gamma, nuclear extracts were also purified from IFN-gamma treated cells. Our data indicate that a) nuclear binding proteins (named IFN-gamma-B3 and Z-B1/B2) are detectable, specific for the IFN-gamma and Z boxes of the human HLA-DR alpha gene; b) both IFN-gamma-B3 and Z-B1/B2 are present in HLA-D negative cell lines and c) the content of IFN-gamma-B3 and Z-B1/B2 is not modulated by IFN-gamma treatment. These data suggest that the presence in the nuclear compartment of these factors, presumably necessary for the correct regulation of the HLA-DR alpha gene, is not sufficient to explain its differential constitutive and induced expression in a variety of in vitro cultured cell lines of different lineage.

Base Sequence↗
PubMedDate not supplied

DNA methylation of the Ha-ras-1 oncogene in neoplastic cells.

The DNA methylation pattern of the human Ha-ras-1 oncogene and the levels of specific mRNA have been analysed in established tumor cell lines and in surgical biopsies. In long-term cultures, the Ha-ras-1 gene is hypomethylated at its 5' end and highly methylated at its 3' portion. The GCGC sites at the 5' end have been shown to become methylated only when E. Coli HhaI methylase is added to isolated DNA, while they remain unmethylated when the enzyme is added to chromatin. These data indicate that the 5' portion of this protooncogene is maintained physiologically unmethylated, possibly because it is necessary for gene transcription. Along the same line of evidence, when levels of mRNA and methylation of the gene were comparatively analysed in breast tumors and autologous normal mammary tissue, no appreciable differences in the degree of methylation were found despite significant differences in mRNA content. These findings show that the levels of Ha-ras- mRNA are independent of the DNA methylation state.

Breast Neoplasms↗