Adenovirus E1A specifically blocks SWI/SNF-dependent transcriptional activation

Area of Science:

• Molecular Biology
• Yeast Genetics
• Virology

Background:

• Adenovirus E1A oncoprotein is a key viral factor in cellular transformation.
• E1A's N-terminal and CR1 domains are crucial for its oncogenic functions, including p300 binding.
• Understanding E1A's mechanism of action can provide insights into viral oncogenesis and host cell manipulation.

Purpose of the Study:

• To identify host factors in Saccharomyces cerevisiae required for adenovirus E1A243 oncoprotein function.
• To elucidate the role of the SWI/SNF transcriptional regulatory complex in mediating E1A's cellular effects.
• To investigate the conserved nature of E1A-SWI/SNF interactions across species.

Main Methods:

• Genetic screening in S. cerevisiae to identify genes essential for E1A243-induced slow growth.
• Gene mutation analysis of SWI/SNF complex components.
• Assessment of E1A's effect on the transcriptional activation of specific genes (INO1, SUC2).

Main Results:

• A genetic screen identified SNF12, a subunit of the SWI/SNF complex, as essential for E1A243 function.
• Mutations in other SWI/SNF components also abrogated E1A's slow-growth phenotype.
• E1A expression specifically inhibited the SWI/SNF-dependent transcriptional activation of INO1 and SUC2 genes.

Conclusions:

• The SWI/SNF transcriptional regulatory complex is a direct target of the adenovirus E1A243 oncoprotein.
• E1A243 interferes with SWI/SNF-mediated gene activation, contributing to its cellular effects.
• This functional interaction between E1A and SWI/SNF is conserved between yeast and mammalian cells.