Adenovirus as a Model for Control of Gene Expression 
We are currently mapping the domains on ElA 
and YY-1 through which they interact. The loca- 
tion of these domains might provide insight to 
the mechanism by which the viral activator alters 
YY-1 function. We are also searching for cellular 
proteins that might interact with the domain of 
YY-1 responsible for repression. 
^ The P5 promoter of the adeno-associated virus 
contains two binding sites for YY- 1 . The site that 
was originally studied is centered about 60 base 
pairs upstream of the transcriptional initiation 
site, and it is responsible for the repression and 
ElA-mediated activation discussed above. The 
second site is centered at the P5 transcriptional 
control region. Its location suggested that YY-1 
might serve an initiator function in addition to its 
repression function. Short DNA sequences 
surrounding several transcriptional start sites 
have been shown to be capable of starting tran- 
scription and have been termed initiator ele- 
ments. These sequences can direct RNA polymer- 
ase to initiate transcription at the correct start site 
in the absence of any other binding sites for 
known transcription factors. When binding sites 
for additional factors are added, the initiator se- 
quences become much more efficient. 
The binding site for YY- 1 proved to behave as 
an initiator element. Furthermore, by studying its 
activity in cell-free extracts and using antibodies 
specific for YY- 1 , we were able to show that YY- 1 
protein is required for the initiator activity dis- 
played by its binding site. Work in progress to 
determine whether YY- 1 interacts with other pro- 
teins in the initiation complex should elucidate 
its role in transcription. 
It is intriguing that YY- 1 (Yin and Yang factor 
1 ) is able to exert opposite effects when it binds 
to different locations within a promoter. In the 
adeno-associated virus promoter, it represses 
transcription when bound upstream of the start 
site, and it contributes in a positive sense to the 
initiation event when bound at the start site. Our 
longer term goal will be to understand how the 
factor can mediate these two different activities. 
Finally, it is important to note that in addition 
to activating transcription through YY-1 and 
other cellular transcription factors, the ElA pro- 
tein can oncogenically transform cells. Almost 
certainly, at least part of its oncogenic activity 
results from its ability to bind to proteins such as 
the cellular retinoblastoma protein, a recessive 
oncogene product whose proper function is re- 
quired for appropriate growth regulation of cells. 
It is possible, however, that interactions of ElA 
protein with transcriptional regulatory proteins 
also contribute to oncogenesis. Work is in 
progress to determine whether alteration of 
YY-1 function can play a role in cellular 
transformation. 
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