Adenovirus E1A Specifically Blocks SWI/SNF-Dependent Transcriptional Activation

Abstract

Expression of the adenovirus E1A₂₄₃ oncoprotein in Saccharomyces cerevisiae produces a slow-growth phenotype with accumulation of cells in the G, phase of the cell cycle. This effect is due to the N-terminal and CR1 domains of E1A₂₄₃, which in rodent cells are involved in triggering cellular transformation and also in binding to the cellular transcriptional coactivator p300. A genetic screen was undertaken to identify genes required for the function of E1A₂₄₃ in S. cerevisiae. This screen identified SNF12, a gene encoding the 73-kDa subunit of the SWI/SNF transcriptional regulatory complex. Mutation of genes encoding known members of the SWI/SNF complex also led to loss of E1A function, suggesting that the SWI/SNF complex is a target of E1A₂₄₃. Moreover, expression of E1A in wild-type cells specifically blocked transcriptional activation of the INO1 and SUC2 genes, whose activation pathways are distinct but have a common requirement for the SWI/SNF complex. These data demonstrate a specific functional interaction between E1A and the SWI/SNF complex and suggest that a similar interaction takes place in rodent and human cells.