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We used a systems biology approach to identify host transcriptional networks in such cells and study the concentration-dependent changes produced by HPV16-E6 and -E7 oncoproteins. We investigated sample sets derived from the W12 model of cervical neoplastic progression, for which high quality phenotype\/genotype data were available. We defined a gene co-expression matrix containing a small number of highly-connected hub nodes that controlled large numbers of downstream genes (regulons), indicating the scale-free nature of host gene co-expression in W12. We identified a small number of \u2018master regulators\u2019 for which downstream effector genes were significantly associated with protein levels of HPV16 E6 (n\u2009=\u20097) or HPV16 E7 (n\u2009=\u20095). We validated our data by depleting E6\/E7 in relevant cells and by functional analysis of selected genes<jats:italic>in vitro<\/jats:italic>. We conclude that the network of transcriptional interactions in HPV16-infected basal-type cervical epithelium is regulated in a concentration-dependent manner by E6\/E7, via a limited number of central master-regulators. These effects are likely to be significant in cervical carcinogenesis, where there is competitive selection of cells with elevated expression of virus oncoproteins.<\/jats:p>","DOI":"10.1038\/srep29832","type":"journal-article","created":{"date-parts":[[2016,7,26]],"date-time":"2016-07-26T09:04:26Z","timestamp":1469523866000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Identification of host transcriptional networks showing concentration-dependent regulation by HPV16 E6 and E7 proteins in basal cervical squamous epithelial cells"],"prefix":"10.1038","volume":"6","author":[{"given":"Stephen P.","family":"Smith","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cinzia G.","family":"Scarpini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian J.","family":"Groves","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard I.","family":"Odle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas","family":"Coleman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,7,26]]},"reference":[{"key":"BFsrep29832_CR1","doi-asserted-by":"publisher","first-page":"527","DOI":"10.1002\/path.4496","volume":"235","author":"IJ Groves","year":"2015","unstructured":"Groves, I. 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