Interaction of Papillomavirus E2 Protein with the Brm Chromatin Remodeling Complex Leads to Enhanced Transcriptional Activation

Abstract

Papillomavirus E2 is a sequence-specific DNA binding protein that regulates transcription and replication of the viral genome. The transcriptional activities of E2 are typically evaluated by transient transfection of nonreplicating E2-dependent reporters. We sought to address whether E2 activates transcription in an episomal context and its potential interaction with the chromatin remodeling proteins. Using an Epstein-Barr virus-based episomal reporter, we demonstrate that E2 stimulates transcription from an E2-dependent promoter in a chromatin context. This activation is enhanced by the presence of proteins associated with SWI/SNF complexes, which are ATP-dependent chromatin remodeling enzymes. We show that exogenous expression of the Brm ATPase enhances E2 activity in SWI/SNF-deficient cell lines and that the amino-terminal transactivation domain of E2 mediates association with the Brm complex in vivo. Using chromatin immunoprecipitation assays, we demonstrate that Brm enhances promoter occupancy by E2 in an episomal context. Our results demonstrate that E2 activates transcription from an episomal reporter system and reveal a novel property of E2 in collaborating with the Brm chromatin remodeling complex in enhancing transcriptional activation.