Analysis of the overexpression of a newly found gene toothrin in Drosophila

A newly found locus of the Drosophila melanogaster genome, named toothrin (tth) has been used to study the role of the conserved the 2/3 domain of genes from the d4 family. In contrast to all vertebrates studied (including humans), in which the 2/3 domain is always accompanied by the d4 domain, the tth gene contains the sequence encoding the 2/3 domain but lacks that encoding the d4 domain. The tth gene overexpression has been studied using the two-component system UAS-GAL4. It has been demonstrated that the tth overexpression at the third-instar larval (prepupal) stage decreases survival rate, simultaneously causing a substantial deceleration of development in Drosophila. It is known that the change of developmental stages in Drosophila is controlled by the rates of the expression of ecdysteroid and juvenile hormones (JHs). It is supposed that the overexpression of the tth gene causes either a shift in the ecdysterone-to-JH ratio (through a decreased JH decay rate or a delayed initiation of ecdysone synthesis) or a deceleration of the release of ecdysterones synthesized

Expression pattern of dd4, a sole member of the d4 family of transcription factors in Drosophila melanogaster

In vertebrates, three members of the d4 gene family code for proteins, which are believed to function as transcription factors and involved in regulation of various intracellular processes. One member of the family, ubi-d4/requiem is ubiquitously expressed gene and two other, neuro-d4 and cer-d4, are expressed predominantly in the neural tissues (Nucleic Acids Res. 20 (1992) 5579; Biochim. Biophys. Acta 14 (1992) 172; Mamm. Genome 11 (2000) 72; Mamm. Genome 12 (2001) 862). Typically, d4 proteins show distinct domain organisation with domain 2/3 in the N-terminal, Krüppel-type zinc finger in the central and two adjacent PHD-fingers (d4-domain) in the C-terminal part of the molecule. However, alternative splicing, which is responsible for complex expression patterns of both neurospecific members of the family, generates multiple protein isoforms lacking certain domains (Nucleic Acids Res. 20 (1992) 5579; Genomics 36 (1996) 174; Mamm. Genome 11 (2000) 72; Mamm. Genome 12 (2001) 862). Exact function of d4 proteins is unclear but their involvement in regulation of differentiation and apoptotic cell death has been proposed (J. Biol. Chem. 269 (1994) 29515; Mamm. Genome 11 (2000) 72; Mamm. Genome 12 (2001) 862). Here we identified a single gene, dd4, in the genome of Drosophila melanogaster, the protein product of which could be assigned to the d4 family. Expression of dd4 is regulated during Drosophila development, and is most prominent in syncytial embryos and later in the embryonic nervous and reproductive systems. In flies dd4 mRNA is found in most tissues but the highest level of expression is detected in ovaries

Structure and expression of two members of the d4 gene family in mouse

The d4 family is a group of unique, evolutionarily conserved zinc finger proteins that are involved in the determination of cell fate. The first member of the d4 family, neuro-d4, was cloned as a neurospecific, developmentally regulated rat gene (Buchman et al. 1992). Multiple neuro-d4 mRNAs generated by alternative splicing give rise to a set of structurally unique proteins. The most characteristic feature of these proteins is a cysteine/histidine-rich C-terminal d4-domain, a double-paired finger motif that consists of two tandemly arranged PHD finger domains. PHD fingers (Cx2CxnCx2Cx4Hx2CxnCx2C) have some structural similarity to the LIM domain and RING fingers and are hallmarks of many transcription co-activators/repressors (Aasland et al. 1995; Saha et al. 1995). A single Kru¨ppel-type zinc finger was found in the N-terminal part of the neuro-d4 protein molecule, but some neurod4 proteins lack this finger along with a nuclear localization signal and a stretch of negatively charged amino acids. Studies of the gene structure and expression suggested that the neuro-d4 proteins are neurospecific nuclear factors, although some of these proteins could have cytoplasmic function(s) (Buchman et al. 1992)

Cerd4, third member of the d4 gene family: expression and organization of genomic locus

Two members of the d4 family of presumptive transcription modulators, neuro-d4 (Neud4) and ubi-d4/Requiem (Req), have been characterized previously. We cloned and characterized the third member of this gene family, cer-d4 (Cerd4), from chicken and mouse cDNA libraries. The expression patterns of Cerd4 gene in both species are similar and more restricted than expression patterns of other two d4 genes. The main sites of Cerd4 expression are retina and cerebellum, where multiple transcripts could be detected. Two major types of Cerd4 proteins are a full-length isoform possessing all domains characteristic to the d4 family and truncated XZ isoform without C-terminal tandem of PHD fingers. The developmental kinetics of expression of these isoforms is different. The intron/exon structure of human Cerd4 gene is similar to that of neuro-d4 and ubi-d4/Requiem genes, but most introns of Cerd4 gene are much larger than the corresponding introns of the other two genes