Different papillomaviruses have different repertoires of transcription factor binding sites: convergence and divergence in the upstream regulatory region

Garcı́a-Vallvé, Santiago; Iglesias-Rozas, José R.; Alonso, Ángel; Bravo, Ignacio G.

doi:10.1186/1471-2148-6-20

Cited by 30 publications

(15 citation statements)

References 32 publications

(44 reference statements)

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“…Likewise, some TFs such as EPOC-1/Skn-1a, C/EBP-α, -β, c-Myb, NFATx, Pax5, and WT1, have been reported to be involved in differentiation dependent expression of early and late viral genes, [ 26 ]. Moreover, LCRs of different HPV types contain distinctive potential TF binding sites, which could be associated to viral expression patterns associated to each viral type, in response to host-cell differentiation [ 27 ]. For example, it has been shown that GATA3 and TFAP2B specifically affect HPV18 transcription, while no such binding sites are present in the HPV16-LCR [ 28 ].…”

Section: Introductionmentioning

confidence: 99%

SOX2 as a New Regulator of HPV16 Transcription

Martínez-Ramírez

del-Castillo-Falconi

Mitre-Aguilar

et al. 2017

Viruses

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Persistent infections with high-risk human papillomavirus (HPV) constitute the main risk factor for cervical cancer development. HPV16 is the most frequent type associated to squamous cell carcinomas (SCC), followed by HPV18. The long control region (LCR) in the HPV genome contains the replication origin and sequences recognized by cellular transcription factors (TFs) controlling viral transcription. Altered expression of E6 and E7 viral oncogenes, modulated by the LCR, causes modifications in cellular pathways such as proliferation, leading to malignant transformation. The aim of this study was to identify specific TFs that could contribute to the modulation of high-risk HPV transcriptional activity, related to the cellular histological origin. We identified sex determining region Y (SRY)-box 2 (SOX2) response elements present in HPV16-LCR. SOX2 binding to the LCR was demonstrated by in vivo and in vitro assays. The overexpression of this TF repressed HPV16-LCR transcriptional activity, as shown through reporter plasmid assays and by the down-regulation of endogenous HPV oncogenes. Site-directed mutagenesis revealed that three putative SOX2 binding sites are involved in the repression of the LCR activity. We propose that SOX2 acts as a transcriptional repressor of HPV16-LCR, decreasing the expression of E6 and E7 oncogenes in a SCC context.

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Section: Introductionmentioning

confidence: 99%

SOX2 as a New Regulator of HPV16 Transcription

Martínez-Ramírez

del-Castillo-Falconi

Mitre-Aguilar

et al. 2017

Viruses

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“…The viral long control region (LCR) comprises approximately 10% of the viral genome and encloses cis-regulatory elements for cellular and viral transcription factors (TFs) that modulate early gene expression and replication [ 11 ]. The repertoire of potential TFs binding sites within the LCR vary largely among distinct HPV types and variants [ 12 , 13 ] due to nucleotide divergences, and may impact binding affinity, transcriptional activity and ultimately the clinical outcome associated with HPV infections [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

Differences in Transcriptional Activity of Human Papillomavirus Type 6 Molecular Variants in Recurrent Respiratory Papillomatosis

et al. 2015

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A significant proportion of recurrent respiratory papillomatosis (RRP) is caused by human papillomavirus type 6 (HPV-6). The long control region (LCR) contains cis-elements for regulation of transcription. Our aim was to characterize LCR HPV-6 variants in RRP cases, compare promoter activity of these isolates and search for cellular transcription factors (TFs) that could explain the differences observed. The complete LCR from 13 RRP was analyzed. Transcriptional activity of 5 variants was compared using luciferase assays. Differences in putative TFs binding sites among variants were revealed using the TRANSFAC database. Chromatin immunoprecipation (CHIP) and luciferase assays were used to evaluate TF binding and impact upon transcription, respectively. Juvenile-onset RRP cases harbored exclusively HPV-6vc related variants, whereas among adult-onset cases HPV-6a variants were more prevalent. The HPV-6vc reference was more transcriptionally active than the HPV-6a reference. Active FOXA1, ELF1 and GATA1 binding sites overlap variable nucleotide positions among isolates and influenced LCR activity. Furthermore, our results support a crucial role for ELF1 on transcriptional downregulation. We identified TFs implicated in the regulation of HPV-6 early gene expression. Many of these factors are mutated in cancer or are putative cancer biomarkers, and must be further studied.

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“…Weak bands were not scored. The genetic similarity between individual pairs of genotypes was analyzed by DendroUPGMA software [38] based on the unweighted pair-group method with arithmetic means. The Dice coefficient was employed to estimate genetic similarity.…”

Section: Data Scoring and Analysismentioning

confidence: 99%

Genetic diversity of maize germplasm assessed by retrotransposon‐based markers

et al. 2014

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Maize is one of the most important crops and also a model for grass genome research. Transposable elements comprise over 78% of the maize genome and their ability to generate new copies makes them good potential markers. Interretrotransposon-amplified polymorphism (IRAP) and retrotransposon microsatellite amplified polymorphism (REMAP) protocols were used for the first time in maize to study the genetic variability between maize cultivars. Ten PCR primers were selected based on a systematic analysis of the sequence conservation in the extremities of different high copy number transposable elements, whereas one primer was chosen based on a microsatellite sequence. Of the 16 primer combinations tested, 14 produced polymorphic bands. These markers were used to identify genetic similarity among 20 maize cultivars selected by their different kernel oil content. Genetic similarity analysis was performed based on the polymorphic band profiles and dendrograms were developed by the unweighted pair-group method with arithmetic averages. Clustering technique revealed that samples were grouped into three clusters that differed in their kernel oil content and size, and in their relative embryo size. In the current investigation, there is evidence that IRAP/REMAP may be useful as markers in maize.

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Different papillomaviruses have different repertoires of transcription factor binding sites: convergence and divergence in the upstream regulatory region

Cited by 30 publications

References 32 publications

SOX2 as a New Regulator of HPV16 Transcription

SOX2 as a New Regulator of HPV16 Transcription

Differences in Transcriptional Activity of Human Papillomavirus Type 6 Molecular Variants in Recurrent Respiratory Papillomatosis

Genetic diversity of maize germplasm assessed by retrotransposon‐based markers

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