Mechanisms of Gene Regulation in Animal Cells 
ing the general transcriptional apparatus, we dis- 
covered two components that serve as the func- 
tional bridge between upstream trans-activators 
and the initiation complex. These novel factors 
appear to be part of the missing link that directs 
promoter-selective transcription in animal cells, 
and we anticipate that they will be members of a 
diverse and essential class of regulatory proteins. 
Transcription of Developmentally 
Regulated Genes 
One of our long-term interests is to understand 
mechanisms underlying the regulation and ex- 
pression during development of higher organ- 
isms. We have begun to address this issue in two 
ways: first, by initiating a series of in vitro exper- 
iments aimed at dissecting the transcriptional 
regulation of Drosophila melanogaster genes, 
including alcohol dehydrogenase (Adh), Ultra- 
bithorax (Ubx) , Antennapedia (Antp) , dopa de- 
carboxylase (Ddc), and hunchback. A major 
advance was the development of in vitro tran- 
scription reactions from staged Drosophila em- 
bryos that accurately initiate RNA synthesis and 
recapitulate the temporal program of transcrip- 
tion displayed by these tissue-specific and devel- 
opmentally regulated genes. A second approach 
has been to investigate the regulatory mechanism 
of RNA polymerase initiation factors in vivo. 
Various systems have been adapted to introduce 
altered genes back into cells or whole organisms 
to study their patterns of expression. 
These in vitro and in vivo studies have re- 
cently led to two exciting results. First, a negative 
regulator of a developmentally important gene 
has been identified by direct biochemical means, 
and its mode of operation can now be dissected. 
The finding of specific transcriptional repressors 
is of particular importance, because it is thought 
that an interplay of positive activators and nega- 
tive regulators is seminal to the spatially re- 
stricted patterns of expression observed during 
embryogenesis. 
A second interesting finding arising from our 
studies of Drosophila is the identification and 
subsequent biochemical characterization of a 
transcription factor that appears to govern the ex- 
pression of genes in cells of the central nervous 
system. The gene encoding this neurogenic- 
specific activator has recently been isolated, and 
its structure is expected to reveal interesting in- 
formation. In addition, the use of fruit flies al- 
lows us to probe the developmental and tissue- 
specific function of this neurogenic regulator in a 
rapid and highly informative manner not readily 
accessible in mammalian cells. These studies are 
expected to yield new insights concerning the 
tissue-specific distribution and temporal timing 
of expression during development. 
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