mel's laboratory has also shown that the E74A pro- 
tein binds to these affected puffs, indicating that it 
can directly control their activity. Studies are 
currently under way to define better the regulatory 
function of E74A at the molecular level. 
In addition, efforts are under way in Dr. Thum- 
mel's laboratory to isolate more regulatory genes 
that are controlled by ecdysone. It is hoped that 
these studies will provide further insights into the 
molecular circuitry involved in the transduction of 
the ecdysone signal at the onset of metamorphosis in 
Drosophila. 
Dr. Thummel is also Assistant Professor of Hu- 
man Genetics at the University of Utah School of 
Medicine. 
Articles 
Andres, A.J., and Thummel, C.S. 1992. Hor- 
mones, puffs and flies: the molecular control 
of metamorphosis by ecdysone. Trends Genet 
8:132-138. 
Boyd, L., O'Toole, E., and Thummel, C.S. 1991. 
Patterns of E74A RNA and protein expression at 
the onset of metamorphosis in Drosophila. Devel- 
opment 112:981-995. 
Chen, T., Bunting, M., Karim, F.D., and Thummel, 
C.S. 1992. Isolation and characterization of five 
Drosophila genes that encode an e^s-related DNA 
binding domain. Dev Biol 151:176-191- 
Thummel, C.S. 1992. Mechanisms of transcrip- 
tional timing in Drosophila. Science 255:39-40. 
MOLECULAR GENETIC ANALYSIS OF EARLY DEVELOPMENT 
Shirley M. Tilghman, Ph.D., Investigator 
Parental Imprinting of the Mouse H19 Gene 
Dr. Tilghman's laboratory is studying the mecha- 
nisms that underlie the appropriate development of 
the mammalian embryo. In mammals, development 
requires the contribution of both the maternal and 
paternal genomes, a consequence of the fact that a 
small number of autosomal genes are inherited from 
their parents in differentially active forms. Two ex- 
amples of such genes are the insulin-like growth fac- 
tor II gene (Igf2) and HI 9, which lie within 90 kbp 
of DNA on the distal end of mouse chromosome 7. 
Igf2 encodes a growth factor required for embry- 
onic development and is expressed almost exclu- 
sively from the paternal chromosome, while the 
HI 9 gene is expressed exclusively from the mater- 
nal chromosome. HI 9 is an unusual gene, in that it 
encodes one of the most abundant products of RNA 
polymerase II in the mouse embryo yet does not 
appear to encode a protein product. 
The close physical linkage of these genes in both 
mice and humans was established by pulsed-field 
gel electrophoresis and large DNA cloning in yeast 
artificial chromosome (YAC) vectors. In addition, 
analysis revealed that the two genes are expressed in 
an identical pattern throughout most of develop- 
ment. The one exception to this rule occurs in the 
choroid plexus and leptomeninges, where both 
genes are initially expressed. Shortly before birth 
the H19 gene is silenced and Igf2 is no longer 
imprinted. 
The foregoing led to a model that proposes that 
the imprinting of Igf2 and HI 9 is mediated by a 
competition in cis for common regulatory elements. 
The common regulatory elements would explain 
their very similar patterns of expression during em- 
bryogenesis. The competition is set up by epige- 
netic markings on one or both of the chromosomes, 
presumably placed there during gametogenesis, the 
only time when the chromosomes are apart and can 
be differentially modified. The marking(s) would 
act to favor transcription of Igf2 on the paternal 
chromosome and H19 on the maternal chromo- 
some. The model can accommodate either a single 
mark on only one chromosome, or two different 
marks on the two chromosomes. In the first in- 
stance, the chromosome without the mark would 
transcribe whichever gene is the better competitor 
for the regulatory elements. The mark could then 
act either positively or negatively to facilitate tran- 
scription of the weaker promoter on the other 
chromosome. 
Zonal Expression of a-Fetoprotein 
Transgenes in Adult Mice 
The developmental regulation of the a-fetopro- 
tein (AFP) gene in liver results in high-level expres- 
sion in the fetus, followed by dramatic transcrip- 
tional repression after birth. The postnatal 
repression can be perturbed in vivo by deleting a 
region of DNA between -250 bp and -838 bp from 
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