A unique mitigator sequence determines the species specificity of the major late promoter in adenovirus type 12 DNA

Zock, Christiane; Iselt, A; Doerfler, Walter

doi:10.1128/jvi.67.2.682-693.1993

Cited by 26 publications

(12 citation statements)

References 58 publications

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“…In Ad12-transformed hamster cells, early viral DNA segments were transcribed (26,30). The major late promoter of Ad12 DNA was silenced in hamster cells by a mitigator element (47,48). We examined the cytoplasmic RNAs from a number of Ad12-transformed hamster cell lines and from Ad12-induced hamster tumor cells for the presence of specific transcripts from the Ad12 genome.…”

Section: Resultsmentioning

confidence: 99%

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

Orend

Knoblauch

Kämmer

et al. 1995

J Virol

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

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Section: Resultsmentioning

confidence: 99%

“…Transcription of the E4 region in the tumor line HT5 was very weak. The major late promoter of Ad12 DNA was silenced by a mitigator element(47,48).…”

mentioning

confidence: 99%

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

Orend

Knoblauch

Kämmer

et al. 1995

J Virol

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“…YY1 is a DNA binding transcription factor and it has been found to repress transcription from a variety of cellular promoters, including those from the immunoglobulin K (4), skeletal a-actin (6)(7)(8)(9), c-fos (1O), e-globin (11,12), a-globin (13), y-interferon (14), GM-CSF (15), creatine kinase-M (16), Pdha-2 (17), a-I acid glycoprotein (18), amyloid Al (19), Surfl and 2 (20) and P-casein genes (21,22). Several viruses have also been found to carry YY1 binding sites that have been shown to mediate transcriptional repression: Moloney murine leukemia virus (3), human papillomaviruses (23)(24)(25), Epstein Barr virus (26), human cytomegalovirus (27), human immunodeficiency virus (28), parvovirus (1,29) and adenovirus (30).…”

Section: Introductionmentioning

confidence: 99%

DNA binding sites for the transcriptional activator/repressor YY1

Hyde-DeRuyscher¹,

Jennings²,

Shenk³

1995

Nucl Acids Res

192

162

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YY1 is ubiquitously expressed zinc finger DNA binding protein. It can act as a transcriptional repressor or activator and, when binding at the initiator element, as a component of the basal transcription complex. Binding sites for YY1 have been reported in a wide variety of promoters and they exhibit substantial diversity in their sequence. To better understand how YY1 interacts with DNA and to be able to predict the presence of YY1 sites in a more comprehensive fashion, we have selected YY1 binding sites from a random pool of oligonucleotides. The sites display considerable heterogeneity, but contain a conserved 5'-CAT-3' core flanked by variable regions, generating the consensus 5'-(C/g/a)(G/t)(C/t/a)CATN(T/a)(T/g/c)-3', where the upper case letters represent the preferred base. This high degree of flexibility in DNA recognition can be predicted by modeling the interaction of the four YY1 zinc fingers with DNA and a detailed model for this interaction is presented and discussed.

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“…While the early E1 genes of Ad12 DNA are expressed in abortively infected hamster cells, there is a total block in Ad12 DNA replication (9,18,35) and the transcription of all late viral genes which is attributable to the failure of the Ad12 major late promoter (MLP) to function in hamster cells. A mitigator element in the downstream region of the MLP is likely responsible for the failure of the MLP to function in hamster cells (43,44). The same promoter is operative in permissive human cells.…”

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confidence: 99%

Insufficient levels of NFIII and its low affinity for the origin of adenovirus type 12 (Ad12) DNA replication contribute to the abortive infection of BHK21 hamster cells by Ad12

Schiedner

Doerfler

1996

J Virol

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Human adenovirus type 12 (Ad12) induces undifferentiated sarcomas in neonate Syrian hamsters and hence presents a suitable model for studies of the molecular mechanism of viral oncogenesis. Since we submit that an understanding of the early steps in the interaction between Ad12 and hamster cells might shed light on the initiation of malignant transformation, the abortive infection of BHK21 hamster cells with Ad12 has been investigated in detail. Ad12 replication in these cells is blocked in early stages, while Ad2 can replicate to moderate titers. Early Ad12 genes are expressed in BHK21 hamster cells, but there is a total block in Ad12 DNA replication and late gene transcription. The Ad5-transformed hamster cell line BHK297-C131, with the left terminus of Ad5 DNA chromosomally integrated and constitutively expressed, allows limited levels of Ad12 DNA replication and late transcription, probably through Ad5 E1 functions, but not the translation of late Ad12 gene products. We have now investigated the capacities of binding of nuclear proteins NFI and NFIII from permissive human KB cells, nonpermissive hamster BHK21 cells, and complementing BHK297-C131 cells to the origin of replication (ori) of Ad2 or Ad12 DNA. The electrophoretic mobility shift assay has been used to assess these binding reactions. The data support the notions that NFIII of BHK21 cells has a lower affinity for the ori of Ad12 DNA than for the ori of Ad2 DNA and that the levels of NFIII in BHK21 cells are markedly reduced compared with the levels in the permissive human KB cells or the complementing BHK297-C131 hamster cells. These deficiencies are contributing factors for the abortive infection of BHK21 hamster cells with Ad12. The lack of sufficient levels of NFIII in BHK21 cells is also consistent with the decreased replication capacity of Ad2 in hamster compared with human cell lines.

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A unique mitigator sequence determines the species specificity of the major late promoter in adenovirus type 12 DNA

Cited by 26 publications

References 58 publications

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

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

DNA binding sites for the transcriptional activator/repressor YY1

Insufficient levels of NFIII and its low affinity for the origin of adenovirus type 12 (Ad12) DNA replication contribute to the abortive infection of BHK21 hamster cells by Ad12

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