Multiple subelements within the polyomavirus enhancer function synergistically to activate DNA replication.

Muller, William J.; Dufort, Daniel; Hassell, John A.

doi:10.1128/mcb.8.11.5000

Cited by 46 publications

(56 citation statements)

References 44 publications

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“…2]. AP1 appears to play a critical role in Py aux-2 activity (55,64,65,75). This sequence stimulated SV40 on-core activity even better than did the 21-bp repeats.…”

Section: Resultsmentioning

confidence: 99%

“…Deletion of SV40 aux-2 reduces replication from 2-to 100-fold, depending on experimental conditions (34,35). In Py, aux-2 consists of functionally redundant enhancer elements that stimulate Py replication from 200-to 1,000-fold (64,90). Both aux-1 and aux-2 are auxiliary components, because they are dispensable for replication under some conditions and do not affect the mechanism of replication.…”

mentioning

confidence: 99%

“…Some properties of Py enhancers (aux-2) suggest that they serve the same function in replication and transcription. The ability of an enhancer to stimulate DNA replication generally follows its ability to stimulate transcription (12,37,64,90). Enhancer mutations that affect on activity also affect promoter activity (55,80,84), and the ability of the Py on to function in a particular mouse cell type depends upon its associated enhancer component (6,12,58,74).…”

mentioning

confidence: 99%

“…First, aux-1 and aux-2 must lie proximal to opposite ends of on-core whereas enhancers can lie distal to either end of a promoter, and aux-1 requires strict spatial orientation with respect to on-core (14,35,37,43,66,69). Second, maximum stimulation of on-core occurs with weaker enhancers than required for maximum promoter activity (56,57) and with fewer copies of the same transcription factor binding site (64,90). Third, some mutations in the Py enhancer region can eliminate promoter activity without eliminating on activity (67 pSVori, pSV21core, pSVcore, pSVOd, pSV(-41)core, and pSV(=-)lcore, their parent vector pML-1 (34,35,98), and Py origin sequences ao3core, acore, and ,Bcore (56) have been described elsewhere.…”

mentioning

confidence: 99%

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Specific transcription factors stimulate simian virus 40 and polyomavirus origins of DNA replication.

Guo¹,

DePamphilis²

1992

Mol. Cell. Biol.

102

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The origins of DNA replication (ori) in simian virus 40 (SV40) and polyomavirus (Py) contain an auxiliary component (aux-2) composed of multiple transcription factor binding sites. To determine whether this component stimulated replication by binding specific transcription factors, aux-2 was replaced by synthetic oligonucleotides that bound a single transcription factor. Spl and T-antigen (T-ag) sites, which exist in the natural SV40 aux-2 sequence, provided -75 and -20%, respectively, of aux-2 activity when transfected into monkey cells. In cell extracts, only T-ag sites were active. AP1 binding sites could replace completely either SV40 or Py aux-2. Mutations that eliminated API binding also eliminated AP1 stimulation of replication. Yeast GAL4 binding sites that strongly stimulated transcription in the presence of GAL4 proteins failed to stimulate SV40 DNA replication, although they did partially replace Py aux-2. Stimulation required the presence of proteins consisting of the GAL4 DNA binding domain fused to specific activation domains such as VP16 or c-Jun. These data demonstrate a clear role for transcription factors with specific activation domains in activating both SV40 and Py ori. However, no correlation was observed between the ability of specific proteins to stimulate promoter activity and their ability to stimulate origin activity. We propose that only transcription factors whose specific activation domains can interact with the T-ag initiation complex can stimulate SV40 and Py ori-core activity.Most, if not all, of the eukaryotic origins of DNA replication (on) characterized so far consist of two principal components: the core component that determines where replication begins in the chromosome and in which animal species replication occurs, and one or more auxiliary components that stimulate replication in certain cell types (28,30,96). on-core is the minimal cis-acting sequence required to initiate DNA replication under all conditions; it is analogous to a transcription promoter. on-auxiliary sequences generally consist of transcription factor binding sites that are dispensable under some conditions; they are analogous to transcription enhancers. The purpose of auxiliary components may be to regulate DNA replication by determining when initiation occurs. For example, the polyomavirus (Py) on functions only in those mouse cell types that can activate its enhancer (6,12,58,74). In mammalian chromosomes, active genes are replicated early during S phase while quiescent genes are replicated late (82), and initiation of replication may require specific transcription factors (76) that bind DNA sites where replication begins (11).To elucidate the function of on-auxiliary components in mammals, we turned our attention to the origins of DNA replication in simian virus 40 (SV40) and Py. These two closely related viral chromosomes replicate in the nuclei of mammalian cells and, with the exception of a single viral protein (large tumor antigen [T-ag]), rely entirely on the host to replicate their DNA (13,29)....

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“…2]. AP1 appears to play a critical role in Py aux-2 activity (55,64,65,75). This sequence stimulated SV40 on-core activity even better than did the 21-bp repeats.…”

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Specific transcription factors stimulate simian virus 40 and polyomavirus origins of DNA replication.

Guo¹,

DePamphilis²

1992

Mol. Cell. Biol.

102

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“…However, the stimulation of DNA replication by the auxiliary elements of SV40 and polyomavirus replication is markedly greater than that observed for HPV18 in the present study (up to 100-and 1000-fold for SV40 and polyomavirus, respectively, while it is required at the same stage as E2. Binding of cellular factors to the only of 5-fold at best for HPV 18) (44,45). The auxiliary elements of replication are also commonly involved in the control of viral transcription.…”

Section: Involvement Of Cellular Transcription Elementsmentioning

confidence: 99%

Control of HPV 18 DNA replication by cellular and viral transcription factors

et al. 1995

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Papillomavirus replication in vivo requires the interaction of the virally encoded proteins El and E2 with the origin of replication which is localised in the regulatory region (long control region or LCR) of the viral genome. In genital human papillomaviruses (HPVs), the origin overlaps promoter elements of early transcription. In this study, we analysed the replication of HPV18 DNA using the complete LCR containing mutations in transcription regulatory elements. We found that each of the three E2 binding sites proximal to the AT-rich sequence of the origin contributes to the replication rate of DNA, although not identically. In addition, two sequences important for early transcription, an Spi binding site and the TATA box, were also found to play a role in replication. In contrast, two AP1 binding sites required for the enhancer-mediated activation of early transcription did not affect the replication, while other upstream sequences in the LCR did contribute to the replication efficiency. Our results indicate that besides a core origin of replication containing an AT-rich sequence and three E2 binding sites, auxiliary elements affect HPVl 8 DNA replication in the context of the full length LCR, some of which are important for transcription.

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Activation of polyomavirus DNA replication by yeast GAL4 is dependent on its transcriptional activation domains.

Bennett-Cook

Hassell

1991

The EMBO Journal

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The polyomavirus replication origin contains transcriptional regulatory sequences. To determine how these elements function in DNA replication, and to learn whether a common mechanism underlies the activation of transcription and DNA replication, we tested whether a well‐characterized transcriptional activator, yeast GAL4, was capable of stimulating DNA replication and transcription in the same mammalian cell line. We observed that GAL4 activated polyomavirus DNA replication in mouse cells when its binding site was juxtaposed to the late border of the polyomavirus origin core. Synergistic activation of DNA replication was achieved by multimerization of the GAL4 binding site. Analysis of GAL4 mutant proteins, GAL4 hybrid proteins and mutants of the latter revealed that the activation domains of these transcriptional activators were required to stimulate DNA replication. In agreement with previously published data, the activation domains of GAL4 were also required to enhance transcription in the same mouse cell line. These observations implicate transcriptional activators in Py DNA replication and suggest that similar mechanisms govern the activation of transcription and DNA replication.

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Multiple subelements within the polyomavirus enhancer function synergistically to activate DNA replication.

Cited by 46 publications

References 44 publications

Specific transcription factors stimulate simian virus 40 and polyomavirus origins of DNA replication.

Specific transcription factors stimulate simian virus 40 and polyomavirus origins of DNA replication.

Control of HPV 18 DNA replication by cellular and viral transcription factors

Activation of polyomavirus DNA replication by yeast GAL4 is dependent on its transcriptional activation domains.

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