ADENOVIRUS E1A SPECIFICALLY BLOCKS SWI SNF-DEPENDENT TRANSCRIPTIONAL ACTIVATION/

Expression of the adenovirus E1A(243) oncoprotein in Saccharomyces cer evisiae produces a slow-growth phenotype with accumulation of cells in the G(1) phase of the cell cycle. This effect is due to the N-termina l and CRI domains of E1A(243), which in rodent cells are involved in t riggering cellular transformation and also in binding to the cellular transcriptional coactivator p300. A genetic screen was undertaken to i dentify genes required for the function of E1A(243) in S. cerevisiae. This screen identified SNF12, a gene encoding the 73-kDa subunit of th e SWI/SNF transcriptional regulatory complex. Mutation of genes encodi ng known members of the SWI/SNF complex also led to loss of E1A functi on, suggesting that the SWI/SNF complex is a target of E1A(243). Moreo ver, expression of E1A in wild-type cells specifically blocked transcr iptional activation of the INO1 and SUC2 genes, whose activation pathw ays 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.