High impact information on Hr38

• This response is unusual in that it does not involve direct binding of ecdysteroids to either DHR38 or USP [1].
• X-ray crystallographic analysis of DHR38 reveals the absence of both a classic ligand binding pocket and coactivator binding site, features that seem to be common to all NGFI-B subfamily members [1].
• Using this approach, we isolated three Drosophila genes, designated DHR38, DHR78, and DHR96 [2].
• DHR38 is the Drosophila homolog of NGFI-B and binds specifically to an NGFI-B response element [2].
• Moreover, transfection experiments in Schneider cells show that DHR38 can affect ecdysone-dependent transcription [3].

Biological context of Hr38

• We characterized the molecular structure and expression of the Dhr38 gene and initiated an in vivo analysis of its function(s) in development [4].
• The Dhr38 transcription unit spans more than 40 kb in length, includes four introns, and produces at least four mRNA isoforms differentially expressed in development; two of these are greatly enriched in the pupal stage and encode nested polypeptides [4].
• Genomic organization of DHR38 gene in Drosophila: presence of Alu-like repeat in a translated exon and expression during embryonic development [5].
• The DNA-binding domain with two zinc-fingers, and at least part of the ligand-binding peptide, is coded by the largest middle exon2 in DHR38 and exhibits up to 100% homology in short peptide motifs to its mammalian counterpart, where these domains are split into exons 3, 4, 5, and 6 [5].

Anatomical context of Hr38

• In addition to binding to specific response elements as a monomer, DHR38 interacts with the USP component of the ecdysone receptor complex in vitro, in yeast and in a cell line, suggesting that DHR38 might modulate ecdysone-triggered signals in the fly [4].

Associations of Hr38 with chemical compounds

• This suggests that DHR38 plays a role in the ecdysone response and that more generally NGFI-B type receptors may be able to function as heterodimers with retinoid X receptor type receptors in regulating transcription [3].
• DHR38 is a member of the steroid receptor superfamily in Drosophila homologous to the vertebrate NGFI-B-type orphan receptors [4].

Physical interactions of Hr38

• Although members of the NGFI-B family are thought to function exclusively as monomers, we show that DHR38 and BHR38 in fact interact strongly with USP and that this interaction is evolutionarily conserved [3].

Other interactions of Hr38

• Conversely, none of the compounds tested had a significant effect on the activity of three Drosophila orphan nuclear receptors: DHR38, DHR78 or DHR96 [6].
• Di-RXR-1 can bind in vitro to EcR and DHR38, both known insect USP partners [7].
• Dhr38 alleles cause localized fragility and rupturing of the adult cuticle, demonstrating that Dhr38 plays an important role in late stages of epidermal metamorphosis [4].

Analytical, diagnostic and therapeutic context of Hr38

• In situ hybridization to 0-24 h wholemount embryos showed strong expression of DHR38 in neurogenic regions and in the intestinal tract during embryogenesis, suggesting a spatial and temporal control of transcription, partially analogous to the central nervous system-specific expression of NGFI-B in mammals [5].

References