A Novel YY1-Independent Silencer Represses the Activity of the Human Papillomavirus Type 16 Enhancer

O’Connor, Mark J.; Stünkel, Walter; Zimmermann, Holger; Koh, Choon-Heng; Bernard, Hans‐Ulrich

doi:10.1128/jvi.72.12.10083-10092.1998

Cited by 22 publications

(7 citation statements)

References 46 publications

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“…The 28–102E construct with P 97 showed a surprisingly low activity, which could not be increased if the construct was made longer (1–102E construct; data not shown). This might be because of the presence of a recently identified inhibitory element from nt 7903–15 (O’Connor et al , 1998 ).…”

Section: Discussionmentioning

confidence: 99%

Identification of a new promoter in the early region of the human papillomavirus type 16 genome

Braunstein

Madsen

Gavnholt

et al. 1999

Journal of General Virology

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Transcription of the human papillomavirus type 16 (HPV-16) genome is controlled by several promoters ; the P 97 promoter is considered to be the main one. An additional promoter has been identified within the E7 ORF as well as an antisense promoter just upstream of the L2 ORF. The significance of these promoters for early and late gene expression and their activity related to cell differentiation is not known in detail. Identification of two new, previously undescribed transcription start sites at nt 542 just upstream of the E7 ORF and at nt 611 within the E7 ORF is reported. The promoter responsible for the start site at nt 542 (P 542 ) was active in SiHa, HeLa and C33A cells. Very low promoter activity was found upstream of the nt 611 start site. The E7 protein has previously been shown to be synthesized from a polycistronic mRNA encoding both the E6 and E7 proteins under the control of the P 97 promoter. The data reported in the present paper suggest that promoter P 542 may control synthesis of the E7 oncoprotein from a monocistronic mRNA.

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Section: Discussionmentioning

confidence: 99%

Identification of a new promoter in the early region of the human papillomavirus type 16 genome

Braunstein

Madsen

Gavnholt

et al. 1999

Journal of General Virology

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“…HPV16 LCR (nt 7451 to 101). The enhancer, silencer, and promoter regions are defined according to a previous study (52). The biotinylated DNA probes (probes I, II, and III) used in the DNA pulldown assays are indicated by solid lines.…”

Section: Resultsmentioning

confidence: 99%

The Transcriptional Cofactor VGLL1 Drives Transcription of Human Papillomavirus Early Genes via TEAD1

Mori

Takeuchi

Ishii

et al. 2020

J Virol

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The TEAD family of transcription factors requires associating cofactors to induce gene expression. TEAD1 is known to activate the early promoter of human papillomavirus (HPV), but the precise mechanisms of TEAD1-mediated transactivation of the HPV promoter, including its relevant cofactors, remain unexplored. Here, we reveal that VGLL1, a TEAD-interacting cofactor, contributes to HPV early gene expression. Knockdown of VGLL1 and/or TEAD1 led to a decrease in viral early gene expression in human cervical keratinocytes and cervical cancer cell lines. We identified 11 TEAD1 target sites in the HPV16 long control region (LCR) by in vitro DNA pulldown assays; 8 of these sites contributed to the transcriptional activation of the early promoter in luciferase reporter assays. VGLL1 bound to the HPV16 LCR via its interaction with TEAD1 both in vitro and in vivo. Furthermore, introducing HPV16 and HPV18 whole genomes into primary human keratinocytes led to increased levels of VGLL1, due in part to the upregulation of TEADs. These results suggest that multiple VGLL1/TEAD1 complexes are recruited to the LCR to support the efficient transcription of HPV early genes. IMPORTANCE Although a number of transcription factors have been reported to be involved in HPV gene expression, little is known about the cofactors that support HPV transcription. In this study, we demonstrate that the transcriptional cofactor VGLL1 plays a prominent role in HPV early gene expression, dependent on its association with the transcription factor TEAD1. Whereas TEAD1 is ubiquitously expressed in a variety of tissues, VGLL1 displays tissue-specific expression and is implicated in the development and differentiation of epithelial lineage tissues, where HPV gene expression occurs. Our results suggest that VGLL1 may contribute to the epithelial specificity of HPV gene expression, providing new insights into the mechanisms that regulate HPV infection. Further, VGLL1 is also critical for the growth of cervical cancer cells and may represent a novel therapeutic target for HPV-associated cancers.

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“…9). This element was identified as a 9-bp sequence with a critical core sequence that binds an unknown human transcriptional repressor protein (57). The element is located within the HPV-16 origin of DNA replication between the HPV-16 enhancer and the E6/E7 promoter.…”

Section: Discussionmentioning

confidence: 99%

“…The element is located within the HPV-16 origin of DNA replication between the HPV-16 enhancer and the E6/E7 promoter. In transient-transfection assays, two elements are necessary for efficient repression of the E6/E7 promoter (57).…”

Section: Discussionmentioning

confidence: 99%

A Strong Negative Transcriptional Regulatory Region between the Human Cytomegalovirus UL127 Gene and the Major Immediate-Early Enhancer

Lundquist¹,

Meier

Stinski³

1999

J Virol

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The region of the human cytomegalovirus (CMV) genome between the UL127 open reading frame and the major immediate-early (MIE) enhancer is referred to as the unique region. DNase I protection analysis with human cell nuclear extracts demonstrated multiple protein binding sites in this region of the viral genome (P. Ghazal, H. Lubon, C. Reynolds-Kohler, L. Hennighausen, and J. A. Nelson, Virology 174:18–25, 1990). However, the function of this region in the context of the viral genome is not known. In wild-type human CMV-infected human fibroblasts, cells permissive for viral replication, there is little to no transcription from UL127. We determined that the unique region prevented transcription from the UL127 promoter but had no effect on the divergent MIE promoter. In transient-transfection assays, the basal level of expression from the UL127 promoter increased significantly when the wild-type unique sequences were mutated. In recombinant viruses with similar mutations in the unique region, expression from the UL127 promoter occurred only after de novo viral protein synthesis, typical of an early viral promoter. A 111-bp deletion-substitution of the unique sequence caused approximately a 20-fold increase in the steady-state level of RNA from the UL127 promoter and a 245-fold increase in the expression of a downstream indicator gene. This viral negative regulatory region was also mutated at approximately 50-bp regions proximal and distal to the UL127 promoter. Although some repressive effects were detected in the distal region, mutations of the region proximal to the UL127 promoter had the most significant effects on transcription. Within the proximal and distal regions, there are potential cis sites for known eucaryotic transcriptional repressor proteins. This region may also bind unknown viral proteins. We propose that the unique region upstream of the UL127 promoter and the MIE enhancer negatively regulates the expression from the UL127 promoter in permissive human fibroblast cells. This region may be a regulatory boundary preventing the effects of the very strong MIE enhancer on this promoter.

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A Novel YY1-Independent Silencer Represses the Activity of the Human Papillomavirus Type 16 Enhancer

Cited by 22 publications

References 46 publications

Identification of a new promoter in the early region of the human papillomavirus type 16 genome

Identification of a new promoter in the early region of the human papillomavirus type 16 genome

The Transcriptional Cofactor VGLL1 Drives Transcription of Human Papillomavirus Early Genes via TEAD1

A Strong Negative Transcriptional Regulatory Region between the Human Cytomegalovirus UL127 Gene and the Major Immediate-Early Enhancer

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