GenomeRNAi - a database for RNAi phenotypes and reagents
TitleScreen TitleAssayBiomodelSpecies
Genome-wide siRNA screen identifies SMCX, EP400, and Brd4 as E2-dependent regulators of human papillomavirus oncogene expression. Smith et al. (2010) Human papillomavirus oncogene expression regulation (5) BPV1 E2 protein expressionC33A/BE2/18LCR c4H. sapiens

Abstract

An essential step in the pathogenesis of human papillomavirus (HPV)-associated cancers is the dysregulated expression of the viral oncogenes. The papillomavirus E2 protein can silence the long control region (LCR) promoter that controls viral E6 and E7 oncogene expression. The mechanisms by which E2 represses oncogene expression and the cellular factors through which E2 mediates this silencing are largely unknown. We conducted an unbiased, genome-wide siRNA screen and series of secondary screens that identified 96 cellular genes that contribute to the repression of the HPV LCR. In addition to confirming a role for the E2-binding bromodomain protein Brd4 in E2-mediated silencing, we identified a number of genes that have not previously been implicated in E2 repression, including the demethylase JARID1C/SMCX as well as EP400, a component of the NuA4/TIP60 histone acetyltransferase complex. Each of these genes contributes independently and additively to E2-mediated silencing, indicating that E2 functions through several distinct cellular complexes to repress E6 and E7 expression.

Screen details


Stable Id: GR00197-A-5
Screen title: Human papillomavirus oncogene expression regulation (5)
Assay: BPV1 E2 protein expression
Method: Fluorescence
Scope: Selected genes
Screen type: Cell-based
Species: Homo sapiens
Biosource: Cell line
Biomodel: C33A/BE2/18LCR c4
Library: Dharmacon, Human siGENOME SMARTpool library
Reagent type: siRNA
Score type: Z-score
Cutoff: <= -1.5
Notes: Author-reviewed data