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].

References