The nuclear receptor homologue Ftz-F1 and the homeodomain protein Ftz are mutually dependent cofactors

Nuclear hormone receptors and homeodomain proteins are two classes of transcription factor that regulate major developmental processes. Both depend on interactions with other proteins for specificity and activity. The Drosophila gene fushi tarazu (ftz)y which encodes a homeodomain protein1 (Ftz), is required zygo-tically for the formation of alternate segments in the developing embryo2. Here we show that the orphan nuclear receptor α Ftz-Fl (ref. 3), which is deposited in the egg during oogenesis4, is an obligatory cofactor for Ftz. The two proteins interact specifically and directly, both in vitro and in vivo, through a conserved domain in the Ftz polypeptide. This interaction suggests that other nuclear receptor/homeodomain protein interactions maybe important and common in developing organisms.

[1]  T. Kaufman,et al.  Analysis of larval segmentation in lethal genotypes associated with the antennapedia gene complex in Drosophila melanogaster. , 1981, Developmental biology.

[2]  A. Laughon,et al.  Sequence of a Drosophila segmentation gene: protein structure homology with DNA-binding proteins , 1984, Nature.

[3]  G. Struhl.  Near-reciprocal phenotypes caused by inactivation or indiscriminate expression of the Drosophila segmentation gene ftz , 1985, Nature.

[4]  P. O’Farrell,et al.  The engrailed locus of drosophila: In situ localization of transcripts reveals compartment-specific expression , 1985, Cell.

[5]  S. Carroll,et al.  Zygotically active genes that affect the spatial expression of the fushi tarazu segmentation gene during early Drosophila embryogenesis , 1986, Cell.

[6]  P. O’Farrell,et al.  Establishment and refinement of segmental pattern in the Drosophila embryo: spatial control of engrailed expression by pair-rule genes. , 1987, Genes & development.

[7]  N E Baker,et al.  Molecular cloning of sequences from wingless, a segment polarity gene in Drosophila: the spatial distribution of a transcript in embryos , 1987, The EMBO journal.

[8]  P. Ingham,et al.  Regulation of segment polarity genes in the Drosophila blastoderm by fushi tarazu and even skipped , 1988, Nature.

[9]  H. Krause,et al.  Expression, modification, and localization of the fushi tarazu protein in Drosophila embryos. , 1988, Genes & development.

[10]  P. Sharp,et al.  Cloning of a lymphoid-specific cDNA encoding a protein binding the regulatory octamer DNA motif. , 1988, Science.

[11]  P. Ingham,et al.  Autocatalytic ftz activation and metameric instability induced by ectopic ftz expression , 1989, Cell.

[12]  K. G. Coleman,et al.  Expression of engrailed proteins in arthropods, annelids, and chordates , 1989, Cell.

[13]  M. Scott,et al.  A sequence-specific DNA-binding protein that activates fushi tarazu segmentation gene expression. , 1990, Genes & development.

[14]  R. Palmiter,et al.  Spatial and temporal control elements of the Drosophila engrailed gene. , 1990, Genes & development.

[15]  G. Lavorgna,et al.  FTZ-F1, a steroid hormone receptor-like protein implicated in the activation of fushi tarazu , 1991, Science.

[16]  Susan J. Brown,et al.  A deficiency of the homeotic complex of the beetle Tribolium , 1991, Nature.

[17]  Ruth Lehmann,et al.  Induction of germ cell formation by oskar , 1992, Nature.

[18]  C. Ingles,et al.  Homeodomain-independent activity of the fushi tarazu polypeptide in Drosophila embryos , 1992, Nature.

[19]  M. Petkovich,et al.  FTZ-F1β, a novel member of the Drosophila nuclear receptor family , 1993, Mechanisms of Development.

[20]  C. Thummel,et al.  Potential role for a FTZ-F1 steroid receptor superfamily member in the control of Drosophila metamorphosis. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[21]  L. Pick,et al.  Multiple proteins interact with the fushi tarazu proximal enhancer. , 1993, Molecular and cellular biology.

[22]  Susan J. Brown,et al.  The beetle Tribolium castaneum has a fushi tarazu homolog expressed in stripes during segmentation. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[23]  F. Falciani,et al.  Dax, a locust Hox gene related to fushi-tarazu but showing no pair-rule expression. , 1994, Development.

[24]  C. Thummel,et al.  A molecular mechanism for the stage specificity of the Drosophila prepupal genetic response to ecdysone , 1994, Cell.

[25]  C. Tsai,et al.  Pair-rule expression of the Drosophila fushi tarazu gene: a nuclear receptor response element mediates the opposing regulatory effects of runt and hairy. , 1995, Development.

[26]  A. Michon,et al.  Requirement for Drosophila cytoplasmic tropomyosin in oskar mRNA localization , 1995, Nature.

[27]  R. Evans,et al.  The RXR heterodimers and orphan receptors , 1995, Cell.

[28]  H. Krause,et al.  Patterning of the Drosophila embryo by a homeodomain-deleted Ftz polypeptide , 1996, Nature.

[29]  A. Laughon,et al.  Ftz-F1 is a cofactor in Ftz activation of the Drosophila engrailed gene. , 1997, Development.