High impact information on dl

• This is explained by results showing that dCBP is necessary for dl-mediated activation of the twi promoter [1].
• In this paper, we show that low affinity dl-binding sites restrict target gene expression to the ventralmost regions (presumptive mesoderm), where there are peak levels of dl, while high affinity sites permit expression in ventrolateral regions (mesoderm and mesectoderm) containing intermediate levels of the morphogen [2].
• The dorsal (dl) morphogen gradient initiates the formation of the mesoderm, neuroectoderm, and dorsal ectoderm by setting different limits of regulatory gene expression along the dorsoventral axis of the early Drosophila embryo [2].
• We present evidence that the DNA-binding activity of the dl protein is mediated by the region of homology (the rel domain) conserved in the rel and NF-kappa B proteins [3].
• Here we show that dl is a DNA-binding protein that specifically interacts with distal sequences of the zerknüllt (zen) promoter, one of the genetic targets of the morphogen [3].

Biological context of dl

• The dorsal (dl) nuclear gradient initiates the differentiation of the mesoderm, neuroectoderm, and dorsal ectoderm by activating and repressing gene expression in the early Drosophila embryo [4].
• A missense mutation in the presumptive DNA-binding domain causes a complete lack-of-function phenotype in trans to a deficiency but exerts a dominant-negative effect in trans to a wild-type copy of dl [5].
• Furthermore, the melanotic tumor phenotype of Toll and cactus is not dl dependent [6].
• In addition to its function in embryonic development, the NF-kappa B/rel-related gene dorsal (dl) of Drosophila is expressed in larval and adult fat body where its RNA expression is enhanced upon injury [6].
• The dl concentration gradient is initiated by regulated nuclear transport, and only protein that enters nuclei is active in the D-V patterning process [3].

Anatomical context of dl

• Injury also leads to a rapid nuclear translocation of dl from the cytoplasm in fat body cells [6].
• Mutants that serially delete the 5' flanking region show that removal of the dl binding site inhibited GGN4 gene expression in both A6 cells and Xenopus oocytes [7].

Physical interactions of dl

• The ventral specific repression of dpp transcription is directly mediated by binding sites for the dorsal (dl) morphogen in the repressor elements [8].
• Complex 3 (200 kDa) is a cact protein complex that does not contain dl protein [9].
• Using a combination of promoter fusion-P-transformation assays, and in vitro DNA-binding assays coupled with site-directed mutagenesis, we establish a direct link between dl-binding sites and twi expression in the early embryo [10].

Regulatory relationships of dl

• The nuclear uptake of the dl protein is stimulated by products of the dorsal group genes but inhibited by the cactus (cact) product [5].
• We have found that Toll can enhance the nuclear localization of dl and, independently, the ability of dl to activate transcription once in the nucleus [11].

Other interactions of dl

• Therefore, carboxy-terminal sequences influence the cytoplasmic retention, although a domain of dl-cact interaction residues in the amino-terminal portion [5].
• Evidence is presented that the tor pathway selectively masks the ability of dl to repress gene expression but has only a slight effect on activation [4].
• The dorsal (dl) protein is a member of the Rel family of transcription factors [5].
• Because dpp and zen have nearly coincident early expression domains, these results indicate that the same boundary of repression can be specified by dl-binding sites of different affinity [8].
• In an effort to determine how dl functions as a repressor we have performed a detailed characterization of a zen silencer element, called the VRE, which mediates ventral repression in response to the dl gradient [12].

References