TY - JOUR
T1 - The sequence specificity of homeodomain-DNA interaction
AU - Desplan, Claude
AU - Theis, Jim
AU - O'Farrell, Patrick H.
N1 - Funding Information:
We are grateful to the people in the O’Farrell lab for their support. In particular, we thank Steve DiNardo, Jim Jaynes, Jill Jongens, Bill Kalionis, Delia Lakich, Christian Lehner, and John Little for their valuable comments on the manuscript, and Judy Piccini for handling its editing. We also thank people in the C. Guthrie and K. Yamamoto labs, in particular Shelly Haltiner Jones. We would like to acknowledge open discussions with Matt Scott, Alan Laughon, Tim Hoey, and Mike Le-vine, who have been very generous with material, information, and encouragement. We also thank Phil Beachy, Liz Gavis, Mark Krasnow, and David Hogness for sharing their data on the Ubx protein and its binding sites, Jessica Treisman for the data on the binding of various classes of homeodomains, and Annick Jullienne and M. S. Moukhtar for the calcitonin cDNA and constant encouragement. A special thank you is addressed to Steve DiNardo and Judy Kassis who have been invaluable colleagues and friends who have contributed many ideas during challenging and stimulating discussions. This work was supported by National Institutes of Health and National Science Foundation grants (to I? H. 0.). C. D. was an EMBO fellow, and J. T. was supported by a National Institutes of Health training grant.
PY - 1988/9/23
Y1 - 1988/9/23
N2 - The Drosophila developmental gene, engrailed, encodes a sequence-specific DNA binding activity. Using deletion constructs expressed as fusion proteins in E. coli, we localized this activity to the conserved homeodomain (HD). The binding site consensus, TCAATTAAAT, is found in clusters in the engrailed regulatory region. Weak binding of the En HD to one copy of a synthetic consensus is enhanced by adjacent copies. The distantly related HD encoded by fushi tarazu binds to the same sites as the En HD, but differs in its preference for related sites. Both HDs bind a second type of sequence, a repeat of TAA. The similarity in sequence specificity of En and Ftz HDs suggests that, within families of DNA binding proteins, close relatives will exhibit similar specificities. Competition among related regulatory proteins might govern which protein occupies a given binding site and consequently determine the ultimate effect of cis-acting regulatory sites.
AB - The Drosophila developmental gene, engrailed, encodes a sequence-specific DNA binding activity. Using deletion constructs expressed as fusion proteins in E. coli, we localized this activity to the conserved homeodomain (HD). The binding site consensus, TCAATTAAAT, is found in clusters in the engrailed regulatory region. Weak binding of the En HD to one copy of a synthetic consensus is enhanced by adjacent copies. The distantly related HD encoded by fushi tarazu binds to the same sites as the En HD, but differs in its preference for related sites. Both HDs bind a second type of sequence, a repeat of TAA. The similarity in sequence specificity of En and Ftz HDs suggests that, within families of DNA binding proteins, close relatives will exhibit similar specificities. Competition among related regulatory proteins might govern which protein occupies a given binding site and consequently determine the ultimate effect of cis-acting regulatory sites.
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U2 - 10.1016/0092-8674(88)90123-7
DO - 10.1016/0092-8674(88)90123-7
M3 - Article
C2 - 3046753
AN - SCOPUS:0023729682
SN - 0092-8674
VL - 54
SP - 1081
EP - 1090
JO - Cell
JF - Cell
IS - 7
ER -