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Gene Review

kni  -  knirps

Drosophila melanogaster

Synonyms: CG4717, Dmel\CG4717, KNI, KNIRPS, Kn, ...
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High impact information on kni

  • Here we provide evidence that the resulting gradient of hb protein dictates where the Krüppel, knirps, and giant genes are expressed by providing a series of concentration thresholds that regulate each gene independently [1].
  • Kr activates stripe 5 and represses stripe 6, kni activates stripe 6 and represses stripe 7, and tll activates stripe 7 [2].
  • The consequence of this difference in intron size is that knrl cannot substitute for kni segmentation function, although it gains this ability when expressed from an intronless transgene [3].
  • Here we report the molecular characterization of the kni gene that codes for a member of the steroid/thyroid receptor superfamily of proteins which in vertebrates act as ligand-dependent DNA-binding transcription regulators [4].
  • Sequence analysis of a cDNA clone representing the human retinoic acid receptor homologue showed similarity of the predicted protein to the vertebrate steroid receptors, as well as to the predicted knirps gene product [5].

Biological context of kni

  • Alteration of the arrangement of Bcd binding sites in the kni enhancer element reduces the role of the amino-terminal domain in cooperative DNA binding but increases the effectiveness of the self-inhibitory function [6].
  • In addition, elimination of symmetric pairs of Bcd binding sites in the kni enhancer element reduces both DNA binding and activation by Bcd [6].
  • These experiments provide a mechanistic basis for understanding how kni and knrl link AP patterning to morphogenesis of the L2 vein by orchestrating the expression of a selective subset of vein-promoting genes in the L2 primordium [7].
  • During early embryogenesis, kni functions as a gap gene to control expression of segmentation genes within the abdominal region of the embryo [8].
  • Analysis of the phenotype of a null mutation of dsp1 (dsp1(1)) reveals that the absence of maternal DSP1 results in A4 segmentation defects that are correlated with a diminution of the kni expression domain [9].

Anatomical context of kni

  • Both genes are initially expressed in three identical regions of the blastoderm embryo: in an anterior cap domain, in an anterior stripe and in a posterior broad band linked to the kni gap gene function [10].
  • In contrast, the expression of the second kni homologous gene is restricted to the late embryonic gonads [11].
  • To study short-range transcriptional repressors in cultured cells, we created chimeric tetracycline repressors based on Drosophila transcriptional repressors Giant, Drosophila C-terminal-binding protein (dCtBP), and Knirps [12].

Associations of kni with chemical compounds

  • However, the motifs in Knirps and Hairy did not adopt well-defined structures in TFE/water mixtures as shown by the absence of medium range NOEs and a high proportion of signal overlap [13].
  • In mutations with an increased amount of cell death (knirps; stardust; fork head), this figure approaches 100% [14].

Physical interactions of kni

  • We also demonstrate that the kni activator binds to the stripe 6 enhancer and present evidence for a competitive mechanism of Kr repression of stripe 6 [15].
  • To effect repression, Knirps and other short-range repressors bind the CtBP corepressor, but these repressors also function via CtBP-independent pathways [16].

Regulatory relationships of kni

  • Employing this system, we show that the cad domain functions by activating the expression of the abdominal gap genes knirps (kni) and giant (gt) [17].
  • We show that kni expression is repressed by tll activity, whereas it is directly enhanced by Kr activity [18].
  • In suppressor-of-nanos mutants, knirps and giant are expressed in spite of high Hb levels [19].
  • To test whether these domains function as sources of morphogenetic activity, the stripe 2 enhancer of the pair-rule gene even-skipped (eve) was used to express kni in an ectopic position [20].

Other interactions of kni

  • Mutations in kni and Kr produce complex alterations in the Ubx expression pattern [21].
  • A morphogenetic gradient of hunchback protein organizes the expression of the gap genes Krüppel and knirps in the early Drosophila embryo [22].
  • In vitro, kni protein competes with the homeodomain-containing bcd protein in binding to a 16-base pair target sequence [23].
  • We also present evidence that different concentrations of hb protein are instructive in defining the limits of kni and gt expression within the presumptive abdomen [24].
  • Here we report that DSP1 is also involved in the regulation of the kni gap gene [9].

Analytical, diagnostic and therapeutic context of kni

  • Genetic analysis and cytoplasmic transplantation experiments suggested that these maternal genes are required to generate a 'posterior activity' that is thought to activate the expression of kni (reviewed in ref. 2). The molecular nature of the members of the posterior group is still unknown [4].
  • By using a DNase I footprinting assay, we have purified a factor by DNA affinity chromatography that binds to the minimal enhancer region of the Drosophila knirps gene and subsequently identified the protein as the core histone H2B [25].


  1. Control of Drosophila body pattern by the hunchback morphogen gradient. Struhl, G., Johnston, P., Lawrence, P.A. Cell (1992) [Pubmed]
  2. Gradients of Krüppel and knirps gene products direct pair-rule gene stripe patterning in the posterior region of the Drosophila embryo. Pankratz, M.J., Seifert, E., Gerwin, N., Billi, B., Nauber, U., Jäckle, H. Cell (1990) [Pubmed]
  3. Loss of gene function through rapid mitotic cycles in the Drosophila embryo. Rothe, M., Pehl, M., Taubert, H., Jäckle, H. Nature (1992) [Pubmed]
  4. Abdominal segmentation of the Drosophila embryo requires a hormone receptor-like protein encoded by the gap gene knirps. Nauber, U., Pankratz, M.J., Kienlin, A., Seifert, E., Klemm, U., Jäckle, H. Nature (1988) [Pubmed]
  5. The Drosophila gene knirps-related is a member of the steroid-receptor gene superfamily. Oro, A.E., Ong, E.S., Margolis, J.S., Posakony, J.W., McKeown, M., Evans, R.M. Nature (1988) [Pubmed]
  6. Enhancer sequences influence the role of the amino-terminal domain of bicoid in transcription. Fu, D., Zhao, C., Ma, J. Mol. Cell. Biol. (2003) [Pubmed]
  7. Activation of the knirps locus links patterning to morphogenesis of the second wing vein in Drosophila. Lunde, K., Trimble, J.L., Guichard, A., Guss, K.A., Nauber, U., Bier, E. Development (2003) [Pubmed]
  8. The knirps and knirps-related genes organize development of the second wing vein in Drosophila. Lunde, K., Biehs, B., Nauber, U., Bier, E. Development (1998) [Pubmed]
  9. DSP1 interacts with bicoid for knirps enhancement. Daulny, A., Rappailles, A., Landemarre, L., Locker, D., Decoville, M. Genesis (2003) [Pubmed]
  10. Identical transacting factor requirement for knirps and knirps-related Gene expression in the anterior but not in the posterior region of the Drosophila embryo. Rothe, M., Wimmer, E.A., Pankratz, M.J., González-Gaitán, M., Jäckle, H. Mech. Dev. (1994) [Pubmed]
  11. Three hormone receptor-like Drosophila genes encode an identical DNA-binding finger. Rothe, M., Nauber, U., Jäckle, H. EMBO J. (1989) [Pubmed]
  12. Cell-type specificity of short-range transcriptional repressors. Ryu, J.R., Olson, L.K., Arnosti, D.N. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  13. Structural determinants outside the PXDLS sequence affect the interaction of adenovirus E1A, C-terminal interacting protein and Drosophila repressors with C-terminal binding protein. Molloy, D.P., Barral, P.M., Bremner, K.H., Gallimore, P.H., Grand, R.J. Biochim. Biophys. Acta (2001) [Pubmed]
  14. Embryonic origin of hemocytes and their relationship to cell death in Drosophila. Tepass, U., Fessler, L.I., Aziz, A., Hartenstein, V. Development (1994) [Pubmed]
  15. Positioning adjacent pair-rule stripes in the posterior Drosophila embryo. Langeland, J.A., Attai, S.F., Vorwerk, K., Carroll, S.B. Development (1994) [Pubmed]
  16. Functional similarity of Knirps CtBP-dependent and CtBP-independent transcriptional repressor activities. Ryu, J.R., Arnosti, D.N. Nucleic Acids Res. (2003) [Pubmed]
  17. Zygotic caudal regulation by hunchback and its role in abdominal segment formation of the Drosophila embryo. Schulz, C., Tautz, D. Development (1995) [Pubmed]
  18. Krüppel requirement for knirps enhancement reflects overlapping gap gene activities in the Drosophila embryo. Pankratz, M.J., Hoch, M., Seifert, E., Jäckle, H. Nature (1989) [Pubmed]
  19. A role of polycomb group genes in the regulation of gap gene expression in Drosophila. Pelegri, F., Lehmann, R. Genetics (1994) [Pubmed]
  20. Concentration-dependent patterning by an ectopic expression domain of the Drosophila gap gene knirps. Kosman, D., Small, S. Development (1997) [Pubmed]
  21. A gap gene, hunchback, regulates the spatial expression of Ultrabithorax. White, R.A., Lehmann, R. Cell (1986) [Pubmed]
  22. A morphogenetic gradient of hunchback protein organizes the expression of the gap genes Krüppel and knirps in the early Drosophila embryo. Hülskamp, M., Pfeifle, C., Tautz, D. Nature (1990) [Pubmed]
  23. Competition for overlapping sites in the regulatory region of the Drosophila gene Krüppel. Hoch, M., Gerwin, N., Taubert, H., Jäckle, H. Science (1992) [Pubmed]
  24. Spatial regulation of the gap gene giant during Drosophila development. Kraut, R., Levine, M. Development (1991) [Pubmed]
  25. Periodic binding of individual core histones to DNA: inadvertent purification of the core histone H2B as a putative enhancer-binding factor. Kerrigan, L.A., Kadonaga, J.T. Nucleic Acids Res. (1992) [Pubmed]
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