indicates that the difference in transcriptional activ- 
ity of c-Jun versus v-Jun may be due to the presence 
of a regulatory domain located at the amino-termi- 
nal region of c-Jun. These results suggest that dur- 
ing retroviral transduction a constitutively active 
Jun protein has been generated by deleting a nega- 
tively acting domain. This putative repressor do- 
main may also play a role in the signal-dependent 
induction of c-Jun activity. Deletions and point mu- 
tants of Jun identify an activation domain rich in 
acidic and proline residues toward the carboxyl-ter- 
minal end of the molecule in a region adjacent to 
the DNA-binding domain. 
III. Identification of a Novel Type of Proline-rich 
Activator. 
Human CTF/nuclear factor I (NF-I) consists of a 
family of CCAAT box binding proteins that activate 
both transcription and DNA replication. Analysis of 
cDNA mutants expressed in Escherichia coli and 
Drosophila cells reveals that the amino-terminal 
portion of CTF-1 is sufficient for site-specific DNA 
recognition, protein dimerization, and adenovirus 
replication. In contrast, transcriptional activation 
requires an additional carboxyl-terminal domain. 
Furthermore, this transcription domain efficiently 
activates a heterologous promoter, such as SV40, 
when fused to the DNA-binding domain of Spl. 
The CTF carboxyl-terminal region consists of an un- 
usual type of transcriptional activation domain con- 
taining —25% proline residues. Dr. Tjian and his 
colleagues propose that this proline-rich domain 
represents a novel class of activators that is distinct 
from activators containing either acidic or gluta- 
mine-rich activation motifs. This indicates that tran- 
scriptional activation is likely to be mediated by sev- 
eral different mechanisms. In addition, these results 
suggest that the interactions, and consequently the 
mechanisms, governing transcriptional activation 
by CTF are distinct from those mediating DNA repli- 
cation. 
IV Mechanism for Negative Regulation in the Dro- 
sophila Embryo. 
The even-skipped (eve) gene is a homeodomain- 
encoding gene that is a genetically defined repres- 
sor of Ultrabithorax {Ubx), fushi tarazu (ftz), and 
wingless (wg). Recently, Dr. Tjian and his col- 
leagues have shown that purified eve protein re- 
presses transcription in vitro at the Ubx promoter, 
in a DNA-binding site-dependent manner. The eve 
protein represses transcription when bound either 
upstream or downstream of the RNA start site or 
when DNA-binding sites are in either orientation. 
Furthermore, eve represses expression from the 
Ubx promoter in Drosophila tissue culture cells, 
again in a binding site-dependent manner. Deletion 
of eve DNA-binding sites does not alter transcrip- 
tion in the absence of eve; thus repression is 
not likely to be the result of eve competitively in- 
hibiting an activator protein from binding to the 
same DNA element. Instead, Dr. Tjian proposes 
that eve protein is probably interfering with the 
function of proteins bound at other locations in the 
promoter. The biochemical demonstration that a 
Drosophila homeodomain protein can directly reg- 
ulate RNA synthesis strengthens the view that these 
regulators act as transcription factors to control de- 
velopment. 
V Analysis of a Developmentally Regulated Dro- 
sophila Transcription Factor Involved in Neuronal 
Gene Expression. 
In an effort to characterize sequence-specific 
transcription factors that regulate gene expression 
during Drosophila development, Dr. Tjian and his 
colleagues have identified and purified a novel 
DNA-binding activity [neurogenic element binding 
transcription factor 1 (NTF-1)]. The purified pro- 
tein consists of several polypeptides that bind se- 
lectively to a functionally important cis-control ele- 
ment of the Ubx promoter and to the neurogenic 
elements of both the dopa carboxylase (Ddc) and 
ftz promoter/enhancer regions. Purified NTF-1 acti- 
vates transcription in vitro in a binding site-depen- 
dent manner through upstream sequences of the 
Ubx promoter. A cDNA clone encoding the open 
reading frame of NTF-1 was isolated, and the de- 
duced primary amino acid sequence of NTF-1 in- 
cludes a glutamine-rich region reminiscent of the 
transcriptional activation domains found in Spl but 
no recognizable DNA-binding domain. NTF-1 ex- 
pression is temporally regulated during embryonic 
development. In addition, in situ hybridization ex- 
periments revealed that NTF-1 is transcribed in a 
spatially restricted pattern in the embryo, with the 
highest level of expression observed in the epider- 
mis and a subset of cells in the central nervous 
system. 
Expression of the NTF-1 cDNA in mammalian 
cells yields a protein that displays DNA-binding and 
transcriptional activities indistinguishable from 
those of the collection of proteins isolated from 
Continued 
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