Heterodimeric Drosophila gap gene protein complexes acting as transcriptional repressors.

The Drosophila gap gene Krüppel (Kr) encodes a transcriptional regulator. It acts both as an integral part of the Drosophila segmentation gene in the early blastoderm and in a variety of tissues and organs at later stages of embryogenesis. In transfected tissue culture cells, the Kr protein (Kr) was shown to both activate and repress gene expression in a concentration‐dependent manner when acting from a single binding site close to the promoter. Here we show that KR can associate with the transcription factors encoded by the gap genes knirps (kni) and hunchback (hb) which affect KR‐dependent gene expression in Drosophila tissue culture cells. The association of DNA‐bound hb protein or free kni protein with distinct but different regions of KR results in the formation of DNA‐bound transcriptional repressor complexes. Our results suggest that individual transcription factors can associate to form protein complexes which act as direct repressors of transcription. The interactions shown here add an unexpected level of complexity to the control of gene expression.

[1]  H. Jäckle,et al.  Functional and conserved domains of the Drosophila transcription factor encoded by the segmentation gene knirps , 1994, Molecular and cellular biology.

[2]  Tom Maniatis,et al.  Transcriptional activation: A complex puzzle with few easy pieces , 1994, Cell.

[3]  R. Tjian,et al.  A glutamine-rich hydrophobic patch in transcription factor Sp1 contacts the dTAFII110 component of the Drosophila TFIID complex and mediates transcriptional activation. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[4]  R. Roeder,et al.  Direct role for Myc in transcription initiation mediated by interactions with TFII-I , 1993, Nature.

[5]  H. Jäckle,et al.  Dimerization and the control of transcription by Krüppel , 1993, Nature.

[6]  R. Roeder,et al.  Unliganded thyroid hormone receptor inhibits formation of a functional preinitiation complex: implications for active repression. , 1993, Genes & development.

[7]  J. Manley,et al.  Transcriptional repression by the Drosophila even-skipped protein: definition of a minimal repression domain. , 1993, Genes & development.

[8]  R. Tjian,et al.  Molecular cloning and functional analysis of Drosophila TAF110 reveal properties expected of coactivators , 1993, Cell.

[9]  H. Jäckle,et al.  Transcriptional regulation and spatial patterning in Drosophila. , 1993, Current opinion in genetics & development.

[10]  H. Jäckle,et al.  Formation of the drosophila larval photoreceptor organ and its neuronal differentiation require continuous Krüppel gene activity , 1992, Neuron.

[11]  D. Reinberg,et al.  Dr1, a TATA-binding protein-associated phosphoprotein and inhibitor of class II gene transcription , 1992, Cell.

[12]  G. Nolan,et al.  The inhibitory ankyrin and activator Rel proteins , 1992, Current Biology.

[13]  Peter A. Lawrence,et al.  Control of Drosophila body pattern by the hunchback morphogen gradient , 1992, Cell.

[14]  M Hoch,et al.  Competition for overlapping sites in the regulatory region of the Drosophila gene Krüppel. , 1992, Science.

[15]  Robert Tjian,et al.  Eukaryotic coactivators associated with the TATA box-binding protein , 1992, Current Biology.

[16]  M Hoch,et al.  Spatial control of the gap gene knirps in the Drosophila embryo by posterior morphogen system. , 1992, Science.

[17]  M. Levine,et al.  Regulation of a segmentation stripe by overlapping activators and repressors in the Drosophila embryo. , 1991, Science.

[18]  R. Roeder,et al.  Family of proteins that interact with TFIID and regulate promoter activity , 1991, Cell.

[19]  H. Jäckle,et al.  Concentration-dependent transcriptional activation or repression by Krüppel from a single binding site , 1991, Nature.

[20]  P. Howley,et al.  The functional BPV-1 E2 trans-activating protein can act as a repressor by preventing formation of the initiation complex. , 1991, Genes & development.

[21]  M. Carey.  Mechanistic advances in eukaryotic gene activation. , 1991, Current opinion in cell biology.

[22]  P. S. Kim,et al.  Modular structure of transcription factors: Implications for gene regulation , 1991, Cell.

[23]  M. Levine,et al.  Transcriptional regulation of a pair-rule stripe in Drosophila. , 1991, Genes & development.

[24]  M. Rosenfeld,et al.  I-POU: a POU-domain protein that inhibits neuron-specific gene activation , 1991, Nature.

[25]  M. Levine,et al.  Activation and repression of transcription by the gap proteins hunchback and Krüppel in cultured Drosophila cells. , 1991, Genes & development.

[26]  R. Roeder,et al.  The complexities of eukaryotic transcription initiation: regulation of preinitiation complex assembly. , 1991, Trends in biochemical sciences.

[27]  Detlef Weigel,et al.  Regulation of Krüppel expression in the anlage of the Malpighian tubules in the Drosophila embryo , 1990, Mechanisms of Development.

[28]  M. Karin,et al.  Transcriptional interference between c-Jun and the glucocorticoid receptor: Mutual inhibition of DNA binding due to direct protein-protein interaction , 1990, Cell.

[29]  K. Yamamoto,et al.  Transcription factor interactions: selectors of positive or negative regulation from a single DNA element. , 1990, Science.

[30]  M Hoch,et al.  cis‐acting control elements for Krüppel expression in the Drosophila embryo. , 1990, The EMBO journal.

[31]  M. Ptashne,et al.  Activators and targets , 1990, Nature.

[32]  B. Lewin.  Commitment and activation at pol II promoters: A tail of protein-protein interactions , 1990, Cell.

[33]  R. Renkawitz,et al.  Transcriptional repression in eukaryotes. , 1990, Trends in genetics : TIG.

[34]  M. Levine,et al.  Transcriptional repression of eukaryotic promoters , 1989, Cell.

[35]  R. Tjian,et al.  Transcriptional regulation in mammalian cells by sequence-specific DNA binding proteins. , 1989, Science.

[36]  M. Krasnow,et al.  Transcriptional activation and repression by Ultrabithorax proteins in cultured Drosophila cells , 1989, Cell.

[37]  M. Beato.  Gene regulation by steroid hormones , 1989, Cell.

[38]  Wolfgang Driever,et al.  The bicoid protein is a positive regulator of hunchback transcription in the early Drosophila embryo , 1989, Nature.

[39]  W. Janning,et al.  The segmentation gene Krüppel of Drosophila melanogaster has homeotic properties. , 1989, Genes & development.

[40]  S. McKnight,et al.  Eukaryotic transcriptional regulatory proteins. , 1989, Annual review of biochemistry.

[41]  H. Jäckle,et al.  Abdominal segmentation of the Drosophila embryo requires a hormone receptor-like protein encoded by the gap gene knirps , 1988, Nature.

[42]  M. Ptashne.  How eukaryotic transcriptional activators work , 1988, Nature.

[43]  P. Ingham.  The molecular genetics of embryonic pattern formation in Drosophila , 1988, Nature.

[44]  Diethard Tautz,et al.  Regulation of the Drosophila segmentation gene hunchback by two maternal morphogenetic centres , 1988, Nature.

[45]  M. Ptashne,et al.  The carboxy-terminal 30 amino acids of GAL4 are recognized by GAL80 , 1987, Cell.

[46]  Diethard Tautz,et al.  Finger protein of novel structure encoded by hunchback, a second member of the gap class of Drosophila segmentation genes , 1987, Nature.

[47]  H. Jäckle,et al.  Structural homology of the product of the Drosophila Krüppel gene with Xenopus transcription factor IIIA , 1986, Nature.