Books and Chapters of Books 
Schoolnik, G.K. 1992. Introduction. In Recombi- 
nant DNA Vaccines: Rationale and Strategy 
(Isaacson, R.E., Ed.). New York: Dekker, pp 11- 
14. 
Articles 
Daley, C.L., Small, P.M., Schecter, G.F., School- 
nik, G.K., McAdam, R. A., Jacobs, W.R., Jr., and 
Hopewell, P.C. 1992. An outbreak of tuberculosis 
with accelerated progression among persons in- 
fected with the human immunodeficiency virus. 
An analysis using restriction-fragment-length poly- 
morphisms. N Engl J Med 326:231-235. 
Giron, J., Ho, A.S., and Schoolnik, G.K. 1991. An 
inducible bundle-forming pilus of enteropatho- 
genic Escherichia coli. Science 254:710-713. 
Hanna, P.C, Mietzner, T.A., Schoolnik, G.K., and 
McClane, B.A. 1991 . Localization of the receptor- 
binding region of Clostridium perfringens en- 
terotoxin utilizing cloned toxin fragments and 
synthetic peptides. The 30 C-terminal amino 
acids define a functional binding region. / Biol 
Chem 266:11037-11043. 
Vuopio-Varkila, J., and Schoolnik, G.K. 1991. Lo- 
cal adherence by enteropathogenic Escherichia 
coli is an inducible phenotype associated with the 
expression of new outer membrane proteins. / 
Exp Med 174:1167-1177. 
Young, V.B., Falkow, S., and Schoolnik, G.K. 1992. 
The invasin protein of Yersinia enterocolitica-. 
internalization of invasin-bearing bacteria by eu- 
karyotic cells is associated with reorganization of 
the cytoskeleton./ Ce// Biol 1 16:197-207. 
ADENOVIRUS GENE EXPRESSION AND ONCOGENESIS 
Thomas E. Shenk, Ph.D., Investigator 
Transcriptional Activation 
by Adenovirus ElA Proteins 
The ElA gene is the first adenovirus gene to be 
expressed when the viral chromosome reaches the 
nucleus of a newly infected cell. The products of the 
ElA gene then activate transcription of all remain- 
ing early viral genes and induce expression of the 
ElA gene itself. The mechanism by which ElA pro- 
teins activate transcription is only partially under- 
stood. However, several cellular transcription fac- 
tors that play roles in the process have been 
identified. 
One of these cellular factors is YYl . A binding site 
for YYl was first identified in the P5 promoter of 
adeno-associated virus, a defective parvovirus that 
depends on a variety of adenovirus gene products — 
including ElA proteins — for its replication. The 
YYl -binding site repressed transcription mediated 
by the P5 promoter as well as heterologous pro- 
moters, and the adenovirus ElAprotein relieved the 
repression and further activated transcription 
through the sequence motif. 
To study the YYl factor better. Dr. Shenk and his 
colleagues cloned its cDNA with a probe DNA corre- 
sponding to an amino acid sequence determined 
from purified protein. YYl is a 4l4-amino acid 
polypeptide that contains four C2H2-type zinc 
fingers, and the sequences of these motifs are re- 
lated to those of the GLI-Kriippel family of DNA- 
binding proteins. 
The binding activity of the cloned YYl protein 
was altered by fusing it to the DNA-binding domain 
of the yeast GAL4 protein. By redirecting the factor 
to a new binding site, it was possible to study the 
activity of the fusion protein in cells that contain 
high endogenous levels of YYl. The fusion protein 
repressed transcription of genes containing a GAL4 
DNA-binding site, and the repression was relieved 
by ElA proteins. Thus the cloned protein displays 
the same biological properties as the activity in 
HeLa ceils that interacts with YYl -binding sites. Fur- 
thermore, since the viral ElA protein would not be 
expected to cause the YYl fusion protein to detach 
from the GAL4 DNA-binding site, it appears likely 
that YYl remains bound to the control region but is 
somehow altered in the presence of ElA proteins so 
that transcription is not repressed. 
The domain of the YYl protein that mediates re- 
pression was mapped by fusing fragments of the 
protein to the GAL4 DNA-binding domain and test- 
ing the ability of the fusion proteins to repress pro- 
moters that contain GAL4 DNA-binding sites. The 
carboxyl-terminal, zinc finger region of the YYl 
protein contained the repression activity. This do- 
main of YYl is also responsible for its ability to bind 
to YYl DNA recognition sites. It is not clear whether 
the zinc fingers are directly involved in the repres- 
sion activity, and, if they are, whether DNA-binding 
and repression functions are mediated by the same 
amino acid sequence. Single amino acid changes are 
110 
