A novel zinc finger gene on human chromosome 1qter that is alternatively spliced in human tissues and cell lines.
DNA-binding proteins that share the conserved C2-H2 zinc finger motif have been shown to have important roles as transcriptional regulators of gene expression and have been implicated in several hereditary human diseases. In order to define potential candidate genes for inherited disorders characterized by aberrant gene expression, we utilized Kruppel-related sequences to isolate zinc finger-containing cDNAs. We isolated and characterized two novel zinc finger-encoding cDNAs from a human hepatoblastoma cell line, which demonstrate DNA sequence homology to a recently described human Kruppel-related gene HZF-3 and appear to be derived from a single gene by alternate mRNA splicing. This gene, denoted "HZF-16," give rise to at least two gene products. One cDNA (i.e., HZF-16.2) has nine zinc finger domains, while alternative splicing of the message gives rise to a smaller product (i.e., HZF-16.1) that has four domains. Despite the internal splicing event, both the 5'- and 3'-untranslated sequences in both cDNAs are identical, as are the first three domains. In the HZF-16.1 cDNA, the fourth zinc finger domain is a fusion product of domains four and nine of HZF-16.2 and could potentially give rise to a new DNA-binding specificity. These alternatively spliced transcripts are differentially regulated in human tissues and transformed cell lines and show a different distribution of expression between human cell lines and normal human tissue. This novel gene was mapped to human chromosome 1q44 by chromosomal in situ suppression hybridization and thus represents a candidate gene for trisomy 1q syndrome and for several other disorders.
Saleh
M
M
Molecular Genetics Laboratory, Salk Institute for Biological Studies, San Diego, CA 92138.
Selleri
L
L
Evans
G A
GA
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002878:Chromosomes, Human, Pair 1; D004247:DNA; D004268:DNA-Binding Proteins / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured; D016335:Zinc Fingers / Q000235:genetics*
D004268:DNA-Binding Proteins; C079654:ZNF124 protein, human; D004247:DNA