family (Jun-D) form homodimers (or heterodimers 
with each other) that bind to an AP-1 site or cAMP 
response element in DNA. However, Fos/Jun or 
Fra-l/Jun heterodimers have much greater affinity 
than Jun homodimers for an AP-1 site. In the 
Fos/Jun heterodimer the basic region of Fos con- 
tributes specific DNA-binding properties equivalent 
to those of Jun. These results support a model in 
which the Fos and Jun basic regions of the Fos/Jun 
heterodimer each interact with symmetrical DNA 
half-sites. 
The laboratory of Assistant Investigator Vikas P 
Sukhatme, M.D., Ph.D. (The University of Chicago) 
has identified novel genes whose expression is con- 
trolled by grov^h factors. One such gene, Egr-1, 
predicts a protein structure characteristic of a tran- 
scriptional regulator, i.e., a molecule capable of reg- 
ulating the expression of a target gene(s). Thus 
these molecules can act as sensors of changes in 
the environment of a cell and serve to transmit and 
convert that information into long-term adaptive 
changes, such as decisions to divide or to differenti- 
ate. 
The work of Associate Investigator Stephen 
A. Liebhaber, M.D. (University of Pennsylvania) 
and his colleagues focuses on the signals that de- 
termine the accuracy of the splicing of the initial 
RNA transcript into a functional mRNA, and the 
signals, both primary sequence and folding (sec- 
ondary structure), that determine how efficiently 
the mRNA is translated into its final protein 
product. In addition, this laboratory is characteriz- 
ing a newly discovered growth hormone gene that 
is specifically expressed by the placenta. This hor- 
mone has activities that suggest it may play an im- 
portant role in fetal growth and/or maternal adap- 
tations. 
The main research interest of Investigator Robert 
Tjian, Ph.D. (University of California at Berkeley) 
and his associates concerns the means by which ge- 
netic information stored in DNA is retrieved in a 
controlled and orderly fashion during the biochem- 
ical process of transcription. They have taken a bio- 
chemical approach to the problem of gene control 
and have devised various means of isolating the in- 
dividual components of the cell responsible for 
transcription. By reconstructing this complex reac- 
tion in the test tube they have been able to study 
how specific genes are turned on and off during 
cell growth and development— mechanisms that 
are of fundamental importance in understanding 
the normal metabolic processes that maintain living 
cells. Dr. Tjian's laboratory has defined novel pro- 
tein structural domains responsible for specificity 
of DNA binding, protein dimerization, and tran- 
scriptional activation; they are exploring promoter- 
selective gene activation in animal cells; and they 
are defining new regulatory factors in the embry- 
onic development of Drosophila and especially its 
nervous system. 
The determination of cellular phenotype is a 
consequence of the control of gene expression in a 
particular cell under a particular set of circum- 
stances. Thus an understanding of the mechanisms 
regulating gene expression, at whatever level it oc- 
curs, is crucial to a final understanding of these 
complex cellular changes. To this end, systems that 
permit the study of transcriptional regulation as 
well as post-transcriptional control of RNA process- 
ing have been utilized by the laboratory of Investi- 
gator Joseph R. Nevins, Ph.D. (Duke University). 
Cellular transcription factors that are the targets of 
viral regulatory proteins and are involved in the 
regulation of transcription of viral and cellular 
genes have been identified and purified. Cell-free 
systems have been established for studying this 
control in vitro, so as to better understand the bio- 
chemical mechanisms involved. A similar approach 
has identified factors involved in the processing of a 
primary transcript to yield a poly (A) site, another 
regulated event of gene expression in animal cells. 
These studies should provide a framework for ex- 
ploring the signaling pathways within cells that ul- 
timately regulate gene expression. 
Assistant Investigator Harinder Singh, Ph.D. (The 
University of Chicago) had previously developed a 
new strategy for isolating genes that encode pro- 
teins that regulate the activities of other genes. 
With this strategy the human gene for a protein 
(Oct-2) that controls the activity of antibody genes 
in B cells was isolated. This laboratory has initiated 
studies on the structure, function, and regulation 
of Oct-2 in antibody-producing cells of the mouse, 
since this system can be manipulated experimen- 
tally. 
Assistant Investigator Gary J. Nabel, M.D., Ph.D. 
(University of Michigan) and his laboratory are in- 
vestigating the molecular regulation of viral and 
cellular genes, with emphasis on the expression of 
human retroviruses in T lymphocytes. Cellular fac- 
tors that control transcription of these genes have 
been defined, including NF-kB, which activates the 
enchancer of the human immunodeficiency virus 
(HIV). Studies of HIV activation and NF-kB in the 
monocyte lineage show that NF-kB is activated at a 
discrete stage of monocyte differentiation and is as- 
Continued 
148 
