Molecular Genetic Studies of Hematopoietic Cells 
clinically important host defense system is regu- 
lated and, more generally, how cell-specific gene 
expression is achieved in this lineage, also de- 
scendent from the pluripotent stem cell. The 
gene under study encodes a subunit of a unique 
cytochrome that is defective in an X-linked con- 
dition, chronic granulomatous disease. By posi- 
tional cloning, we previously isolated the gene, 
determined its structure, and demonstrated the 
presence of the protein product in the cy- 
tochrome complex of phagocytic cells. 
In addition, since interferon-7 stimulates 
phagocytic cell function generally as well as ex- 
pression of the cytochrome, it was also possible 
to show that this lymphokine is clinically effec- 
tive in chronic granulomatous disease. Studies 
have identified several point mutations in the cy- 
tochrome that interfere with protein function in 
vivo and mutations in an associated cytochrome 
subunit encoded by an autosome in rarer cases of 
chronic granulomatous disease. 
More current efforts are directed toward defin- 
ing the elements of the gene responsible for ap- 
proaching regulation in phagocytic cells. 
Through the use of transgenic mice, we identi- 
fied a DNA fragment sufficient for targeting re- 
porters and oncogenes to a subset of phagocytes 
in vivo. Coupled to an oncogene, this fragment 
leads to the consistent development of an in- 
herited malignancy of phagocytes in mice. 
In the promoter we identified a negative regula- 
tory site that binds a protein whose concentration 
falls dramatically during phagocyte differentia- 
tion. This factor corresponds to a putative repres- 
sor termed CCAAT displacement protein (CDP) . 
Through molecular cloning, we have character- 
ized human CDP and shown that it is highly re- 
lated to a novel Drosophila homeobox protein, a 
product of the cut gene, which controls cell fate 
decisions in several tissues during fly develop- 
ment. Although this repressor does not explain 
the restriction of cytochrome expression to 
phagocytic cells, its loss combined with the pres- 
ence of unknown positive, white cell-specific 
regulators very likely accounts for the temporal 
pattern of cytochrome expression during cellular 
maturation. 
More generally, the remarkable similarity of 
human CDP and the fly cut protein suggests func- 
tional correlates and predicts that CDP will partic- 
ipate in cell fate decisions during mammalian 
embryogenesis. Current efforts are directed to 
analysis of the role and function of CDP in mam- 
malian cells and to identification of the critical 
cis- and trans-components responsible for white 
cell-specific gene expression. 
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