Disease relevance of Eip74EF

• Here, we identify the homologue of the Drosophila E75 early ecdysone inducible gene in the yellow fever mosquito Aedes aegypti, and show that, as in Drosophila, the mosquito homologue, AaE75, consists of three overlapping transcription units with three mRNA isoforms, AaE75A, AaE75B, and AaE75C, originating as a result of alternative splicing [1].
• Using a mouse bmi-1 cDNA probe a transcript of 3.3 kb was detected on Northern blots of human Burkitt's lymphoma cell lines [2].
• Facioscapulohumeral muscular dystrophy (FSHD) is a unique dominant disorder involving shortening of an array of tandem 3.3 kb repeats [3].
• Further, we show that the predominant protein binding the purine-rich HTLV-I enhancer element in human T cells is not ets-1 but Elf-1, a member of the ets family which is very similar to the Drosophila morphogen E74 [4].

High impact information on Eip74EF

• The Drosophila 78C early late puff contains E78, an ecdysone-inducible gene that encodes a novel member of the nuclear hormone receptor superfamily [5].
• We have isolated an ecdysone-inducible gene, E74, from the early puff at position 74EF in the Drosophila polytene chromosomes [6].
• We show that E74 consists of three nested transcription units that derive from unique promoters but share a single polyadenylation site [6].
• The 60 kb E74A unit is directly induced by ecdysone and leads to the synthesis of a 6.0 kb mRNA that contains an unusually long 5' leader (1891 nucleotides) with 17 short ORFs [6].
• Within the fifth of the seven E74A introns are two E74B promoters that direct the synthesis of 4.8 and 5.1 kb mRNAs [6].

Biological context of Eip74EF

• We show that E74 can regulate its own transcription, most likely through binding sites within its gene [7].
• A steroid-triggered switch in E74 transcription factor isoforms regulates the timing of secondary-response gene expression [7].
• The steroid-regulated BR-C, E74A and E93 genes are required for salivary gland cell death [8].
• Analysis of the morphological and molecular phenotypes of the double-mutant animals reveals that BR-C and E74 alleles act together to produce both novel and synergistic effects [9].
• One of these fragments shows the highest amino acid sequence homology to the insect ecdysone inducible gene E75 [10].

Anatomical context of Eip74EF

• Although this cell line has previously been shown to synthesize components of the ecdysteroid receptor and ecdysone-inducible proteins, the well-characterized ecdysteroid response element (EcRE) from the Drosophilahsp27 promoter failed to confer a substantial 20-hydroxyecdysone mediated induction in transfected mosquito cells [11].
• Ecdysone-inducible functions of larval fat bodies in Drosophila [12].
• The ratio of Ate1-1 to Ate1-2 mRNA varies greatly among the mouse tissues; it is approximately 0.1 in the skeletal muscle, approximately 0.25 in the spleen, approximately 3.3 in the liver and brain, and approximately 10 in the testis, suggesting that the two R-transferases are functionally distinct [13].
• In early prepupae, when the overall levels of E74A mRNA are decreasing, relatively high levels of E74A RNA persist in the gut, peripodial membranes of the imaginal discs, and proliferation centers of the brain [14].
• Reducing the size of flanking sequence to 3.3 kb of intron 2 restricted lacZ expression to the outflow tract and the basal part of the right ventricle in E10.5 embryos [15].

Associations of Eip74EF with chemical compounds

• It is proposed that the activity of the 20-OH-ecdysone inducible puff 74EF leads to a switch in the synthesis of a transcription factor [16].
• The consensus sequence for E74A protein binding, determined by random-sequence oligonucleotide selection, contains an invariant purine-rich core sequence, C/AGGAA [17].
• A site-directed mutant of apocytochrome c (lysines 5, 7, and 8 replaced by glutamine, glutamic acid, and asparagine) was found to be converted to holocytochrome c (Km approximately 3.3 nM; maximal activity unchanged), even though the mutations completely eliminated the high affinity binding [18].
• We show that a restricted selectivity for GGAA core-containing sites could be conferred to Ets1 upon changing a single lysine residue within CRIII to the threonine found in Elf1 and E74 at this position [19].
• Crithidia fasciculata hsp83 undergoes autophosphorylation on serine and threonine at a rate constant of 3.3 x 10(-3) min-1 [20].

Other interactions of Eip74EF

• As the hormone concentration peaks in late third instar larvae, these transcripts are repressed and the class II RNAs (E74A, E75A and E75B) are induced [21].
• The structure of the DHR3 protein is strikingly similar to that of the MHR3 protein (e.g., 97% amino acid identity for the DNA binding domains), another orphan receptor encoded by an ecdysone-inducible early gene of another insect, Manduca sexta [22].
• We have found that the BR-C is critical for the appropriate regulation of all three classes of ecdysone-inducible genes [23].
• The class I transcripts (E74B and EcR) are induced in mid-third instar larvae in response to the low, but increasing, titer of ecdysone [21].
• The Drosophila 63F early puff contains E63-1, an ecdysone-inducible gene that encodes a novel Ca(2+)-binding protein [24].

Analytical, diagnostic and therapeutic context of Eip74EF

• Northern blot analysis of RNA isolated from staged animals or cultured organs was used to characterize the effects of ecdysone on E74 transcription [25].
• In situ hybridization to polytene chromosomes revealed that these ets-related genes are not clustered in the genome and that only E74 corresponds to an ecdysone-inducible puff locus [26].
• The molecular mass of these bioactive fractions as determined by using gel filtration was in the peptide range of 3.3 to 5.5 kDa [27].

References