purify an 1 1 -kDa protein in a one-to-one molar ratio 
with HNF- 1 . This protein was sequenced and found 
to be a "pioneer"; i.e., it was not related to other 
proteins. Overexpression of the protein activated 
HNF- 1 -dependent transcription by > 100-fold. 
Since the protein is a cofactor for HNF-1, it was 
named DCoH. Further studies have indicated that 
this protein functions by enhancing the stability of 
HNF- 1 dimers and is present within the complex at a 
ratio of 1:1, indicating that normally HNF- 1 is part 
of a heterotetrameric complex. The regulatory po- 
tential for such a heterotetrameric complex could 
be quite large if there is a family of proteins that 
participates in this complex. Hence Dr. Crabtree 
and his colleagues are searching for additional 
members of this complex. 
Dr. Crabtree is also Associate Professor of Pa- 
thology at Stanford University School of Medicine. 
Articles 
Chung, J., Kuo, C.J., Crabtree, G.R., and Blenis, 
J. 1992. Rapamycin-FKBP specifically blocks 
growth-dependent activation of and signaling by 
the 70 kD S6 protein kinases. Cell 69:1227- 
1236. 
Clipstone, N.A., and Crabtree, G.R. 1992. Identifi- 
cation of calcineurin as a key signalling enzyme in 
T-lymphocyte activation. Nature 357:695-697. 
Flanagan, W.M., Corthesy, B., Bram, R.J., and 
Crabtree, G.R. 1991 . Nuclear association of a T- 
cell transcription factor blocked by FK-506 and 
cyclosporin A. Nature 352:803-807. 
Flanagan, W.M., and Crabtree, G.R. 1992. In vitro 
transcription faithfully reflecting T-cell activa- 
tion requirements. /5?o/ Chem 267:399-406. 
Kuo, C.J., Chung, J., Fiorentino, D.F., Flanagan, 
W.M., Blenis, J., and Crabtree, G.R. 1992. Rapa- 
mycin selectively inhibits interleukin-2 activa- 
tion of p70 S6 kinase. Nature 358:71-73. 
Kuo, C.J., Conley, P.B., Chen, L., Sladek, F.M., Dar- 
nell, J.E., Jr., and Crabtree, G.R. 1992. A tran- 
scriptional hierarchy involved in mammalian 
cell-type specification. Nature 355:457-461. 
Mendel, D.B., Khavari, P.A., Conley, P.B., Graves, 
M.K., Hansen, L.P., Admon, A., and Crabtree, 
G.R. 1991. Characterization of a cofactor that reg- 
ulates dimerization of a mammalian homeodo- 
main protein. Science 254:1762-1768. 
Northrop, J.P., Crabtree, G.R., and Mattila, P.S. 
1992. Negative regulation of interleukin 2 tran- 
scription by the glucocorticoid receptor. / Exp 
Med 175:1235-1245. 
Ullman, K.S., Flanagan, W.M., Edwards, C.A., and 
Crabtree, G.R. 1991. Activation of early gene ex- 
pression in T lymphocytes by Oct- 1 and an induc- 
ible protein, OAP^°. Science 254:558-562. 
THE MECHANISM OF A BACTERIAL TRANSPOSITION REACTION 
Nancy L. Craig, Ph.D., Associate Investigator 
Transposition is a recombination reaction in 
which a mobile element translocates between non- 
homologous positions in DNA. Dr. Craig's research 
is focused on understanding the transposition mech- 
anism of the bacterial transposon Tn7. A Tn7 trans- 
position is being defined in molecular terms 
through dissection of the macromolecular interac- 
tions between the proteins mediating this reaction 
and the DNA substrates on which they act. 
The Tn7 transposition machinery is elaborate. 
Tn7 encodes five transposition proteins, TnsA, TnsB, 
TnsC, TnsD, and TnsE; overlapping subsets of these 
proteins mediate Tn7 insertion into alternative 
types of target sites. The Tn7 termini contain com- 
plex arrays of DNA sites that are the DNA substrates 
of this protein machinery. 
A subset of the Tns proteins — TnsA + TnsB + 
TnsC — forms the "core" transposition machinery. 
These proteins execute the DNA strand cleavages 
that separate Tn7 from the donor backbone and the 
strand transfer reactions that subsequently join the 
transposon ends to the target. However, these pro- 
teins alone are inactive; TnsD and TnsE are alterna- 
tive activators of the TnsA + TnsB + TnsC core ma- 
chinery. TnsD activates TnsA + TnsB + TnsC to 
promote high-frequency Tn7 insertion in a specific 
site in the Escherichia coli chromosome called 
attTnl, whereas TnsE provokes these proteins to 
CELL BIOLOGY AND REGULATION 39 
