The initiation of de novo methylation of foreign DNA integrated into a mammalian genome is not exclusively targeted by nucleotide sequence.

摘要: The de novo methylation of foreign DNA integrated into the mammalian genome is a fundamental process whose mechanism has not yet been elucidated. We have studied in adenovirus type 12 (Ad12) genomes inserted Ad12-induced hamster tumor cells. De Ad12 DNA, which methylated virion, initiated two paracentrally located regions and spreads from there across genomes. (i) After extensive cultivation cloned cell lines, same segments different lines become or remain unmethylated, depending on their positions viral genome. (ii) When fragments are transfected cells permanent established by selection for cotransfected neomycin phosphotransferase gene, patterns terminally internally those lines. (iii) A detailed study topology Ad12-transformed T637 A2497-3 tumors T191, T1111(1), T181 performed. Some cellular an orientation colinear with virion genome; others rearranged. An originally segment transposed to left-terminal sequences several tumors. In complete genomes, PstI-D fragment becomes extensively at 5'-CCGG-3' 5'-GCGC-3' sequences. this juxtaposed left-terminal, hypomethylated rearranged remains unmethylated. therefore reason that initiation cannot be directed exclusively nucleotide sequence. Other parameters, such as site integration, conformation integrates, mode selection, chromatin structure related transcriptional activity, may play decisive roles.