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

• Published in: Mammalian genome Vol. 11; no. 1; pp. 72 - 74
• Main Authors: Mertsalov, I B, Kulikova, D A, Alimova-Kost, M V, Ninkina, N N, Korochkin, L I, Buchman, V L
• Format: Journal Article
• Language: English
• Published: United States Springer Nature B.V 01.01.2000
• Subjects: Alternative Splicing - genetics; Amino Acid Sequence; Animals; Base Sequence; Blotting, Northern; d4 gene; DNA - chemistry; DNA Probes - chemistry; Female; Gene Expression Regulation, Developmental; Gene Library; Gene Targeting; Male; Medicin och hälsovetenskap; Mice; Molecular Sequence Data; Multigene Family; neuro-d4 protein; Physical Chromosome Mapping; RNA - chemistry; Sequence Alignment; Sequence Analysis, DNA; Sequence Homology, Amino Acid; Trigeminal Ganglion - chemistry; Zinc Fingers - genetics
• ISSN: 0938-8990; 1432-1777
• DOI: 10.1007/s003350010014

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 (Cx sub(2)Cx sub(n)Cx sub(2)Cx sub(4)Hx sub(2)Cx sub(n)Cx sub(2)C) 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 Krueppel-type zinc finger was found in the N-terminal part of the neuro-d4 protein molecule, but some neuro-d4 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). More recently, two additional members of the neuro-d4 family have been identified in the human, mouse, and chicken genomes (Chestkov et al. 1996; Gabig et al. 1994, 1998). A partial, 5' truncated mouse cDNA for one of these genes, ubi-d4, was cloned and named Requiem by Gabig et al. (1994). In the interleukin-3-dependent myeloid cell line, expression of ubi-d4/Requiem is necessary for apoptosis after withdrawal of IL-3 (Gabig et al. 1994). In contrast, in NGF-dependent neurons, overexpression of neuro-d4 rescues these neurons from death after withdrawal of NGF (our unpublished observation). These results suggest that members of the d4 family participate in regulation of cell survival. However, the exact functions of d4 proteins remain elusive. To further our knowledge about the d4 family, we cloned and characterized mouse genes coding for d4 proteins and studied their expression patterns during embryonic development.