Books and Chapters of Books 
Perrine, S.P., Faller, D.V., Swerdlow, P., Sytkowski, 
A.J., Qin, G., Miller, B.A., Oliveri, N.F., Rudolph, 
A.M., and Kan, Y.W. 1991. Pharmacologic pre- 
vention and reversal of globin gene switching. In 
The Regulation of Hemoglobin Switching (Sta- 
matoyannopoulos, G., and Nienhuis, A.W., Eds.). 
Baltimore, MD: Johns Hopkins University Press, 
pp 425-436. 
Articles 
Cai, S.-P., Eng, B., Kan, Y.W., and Chui, D.H.K. 
1 99 1 . A rapid and simple electrophoretic method 
for the detection of mutations involving small in- 
sertion or deletion: application to (8-thalassemia. 
Hum Genet 87:728-730. 
Chang, J.C., Liu, D., and Kan, Y.W. 1992. A 36- 
base-pair core sequence of locus control region 
enhances retrovirally transferred human /3-globin 
gene expression. Proc Natl Acad Set USA 
89:3107-3110. 
Ikuta, T., and Kan, Y.W. 1991- In vivo protein- 
DNA interactions at the /3-globin gene locus. Proc 
Natl Acad Sci USA 88:10188-10192. 
Kan, Y.W. 1992. Development of DNA analysis for 
human diseases. Sickle cell anemia and thalasse- 
mia as a paradigm. /^vVf^ 267:1532-1536. 
Liu, D., Chang, J.C., Moi, P., Liu, W., Kan, Y.W., 
and Curtin, P.T. 1992. Dissection of the enhancer 
activity of /5-globin 5' DNase I hypersensitive site- 
2 in transgenic mice. Proc Natl Acad Sci USA 
89:3899-3903. 
Rosatelli, M.C., Dozy, A., Faa, V., Meloni, A., Sardu, 
R., Saba, L., Kan, Y.W. , andCao, A. 1992. Molecu- 
lar characterization of /5-thalassemia in the Sardin- 
ian population. Am J Hum Genet 50:422-426. 
STRUCTURAL AND FUNCTIONAL ORGANIZATION OF HOMEOTIC LOCI 
Thomas C. Kaufman, Ph.D., Investigator 
Dr. Kaufman's laboratory continues its efforts to 
understand the regulation and role of the homeotic 
genes during the developmental process in Dro- 
sophila melanogaster. Efforts focus on three 
members of the Antennapedia complex that con- 
trol segmental identity in the head and anterior 
thorax of the embryo and adult: labial (Jab), pro- 
boscipedia (pb), and Sex combs reduced (5cr). 
Each was chosen for its domain of expression and 
accessibility to molecular dissection. 
Additionally, a set of chimeric genes has been con- 
structed that allows ectopic expression of the 
protein products of these three loci as well as 
Deformed {Dfd), Antennapedia {Antp), and Ultra- 
bithorax (Ubx). One set of chimeras utilizes the 
heat-shock-inducible promoter hsp70. 
These chimeras have been used to drive ubiqui- 
tous expression of the homeotic protein products. 
Dr. Josef Heuer has studied the effects of this ex- 
pression on the development of the peripheral ner- 
vous system (PNS) of the embryo. He has found that 
each of the proteins has specific effects on the devel- 
oping PNS, and homeotic proteins normally ex- 
pressed anteriorly (e.g., in the head) have effects on 
the PNS of the abdomen, despite showing no influ- 
ence on the identity of the epidermally derived cuti- 
cle of these same posterior segments. 
Inherent limitations of the heat-shock system have 
led to the utilization of the bipartite system origi- 
nally developed by Dr. Andrea Brand in Dr. Norbert 
Perrimon's group (HHMI, Harvard Medical School). 
The system utilizes constructs encoding the yeast 
GAL4 transcription factor, which can be placed 
downstream of any promoter-enhancer combination 
driving expression in specific and unique patterns. 
The second component involves the UAS target se- 
quences of GAL4, which are now cloned upstream 
of cDNA clones for all of the above-mentioned ho- 
meotics. Dr. Barbara Hamilton has recovered and 
characterized fly stocks containing each of the UAS- 
homeotic constructs. These have been combined 
with two GAL4 lines that are specifically expressed 
in the developing mesoderm and the nervous sys- 
tem, respectively. 
Dr. Hamilton has been able to drive expression of all 
homeotics ectopically and specifically in these tissues. 
This ectopic expression causes either late embryonic or 
larval lethality but is not associated with any striking 
abnormalities in morphogenesis. Any effects on the 
normal expression patterns of the resident homeotic 
loci in either the mesoderm or central nervous system 
(CNS) have yet to be observed. These studies are 
currently extending to an analysis of GAL4 constructs 
driven by the lab and pb promoters. 
GENETICS 207 
