Multiple genes encoding zinc finger domains are expressed in human T cells

Proteins containing zinc finger domains have been implicated in developmental control of gene expression in Drosophila, Xenopus, mouse, and humans. Multiple cDNAs encoding zinc (II) finger structures were isolated from human cell lines of T-cell origin to explore whether zinc finger genes participate in the differentiation of human hematopoietic cells. Initial restriction analysis, genomic Southern blotting, and partial sequence comparisons revealed at least 30 nonoverlapping cDNAs designated cKox(1-30) encoding zinc finger motifs. Analysis of cKox1 demonstrated that Kox1 is a single-copy gene that is expressed in a variety of hematopoietic and nonhaematopoietic cell lines. cKox1 encodes 11 zinc fingers that were shown to bind zinc when expressed as a beta-gal-Kox1 fusion protein. Further analysis of the predicted amino acid sequence revealed a heptad repeat of leucines NH2-terminal to the finger region, which suggests a potential domain for homo- or heterodimer protein formation. On the basis of screening results it was estimated that approximately 70 zinc finger genes are expressed in human T cells. Zinc finger motifs are probably present in a large family of proteins with quite diverse and distinct functions. However, comparisons of individual finger regions in cKox1 with finger regions of cKox2 to cKox30 showed that some zinc fingers are highly conserved in their putative alpha-helical DNA binding region, supporting the notion of a zinc finger-specific DNA recognition code.     

Chelicerate Hox genes and the homology of arthropod segments

Genes of the homeotic complex (HOM-C) in insects and vertebrates are required for the specification of segments along the antero-posterior axis. Multiple paralogues of the Hox genes in the horseshoe crab Limulus poliphemus have been used as evidence for HOM-C duplications in the Chelicerata. We addressed this possibility through a limited PCR survey to sample the homeoboxes of two spider species, Steatoda triangulosa and Achaearanea tepidariorum. The survey did not provide evidence for multiple Hox clusters although we have found apparent duplicate copies of proboscipedia ( pb ) and Deformed ( Dfd   ). In addition, we have cloned larger cDNA fragments of pb, zerknullt ( zen / Hox3 ) and Dfd. These fragments allowed the determination of mRNA distribution by in situ hybridization. Our results are similar to the previously published expression patterns of Hox genes from another spider and an oribatid mite. Previous studies compared spider/mite Hox gene expression patterns with those of insects and argued for a pattern of segmental homology based on the assumption that the co-linear anterior boundaries of the Hox domains can be used as markers. To test this assumption we performed a comparative analysis of the expression patterns for UBX/ABD-A in chelicerates, myriapods, crustaceans, and insects. We conclude that the anterior boundary can be and is changed considerably during arthropod evolution and, therefore, Hox expression patterns should not be used as the sole criterion for identifying homology in different classes of arthropods.     

Isolation and expression of linked zinc finger gene clusters on human chromosome 11q

Proteins that share conserved "zinc finger" motifs represent a class of DNA-binding proteins that have been shown to play a fundamental role in regulating gene expression and to be involved in a number of human hereditary and malignant disease states. We have isolated, characterized, and mapped zinc finger-encoding genes specific to human chromosome 11q to investigate their possible association in the molecular pathogenesis of several disease loci mapped to this chromosome. An arrayed chromosome 11q cosmid library was screened using a degenerate oligonucleotide corresponding to the H/C link consensus sequence of the Drosophila Kruppel zinc finger gene, resulting in the isolation of six putative zinc finger genes. Three of the genes (ZNF123, ZNF125, and ZNF126) were analyzed and shown to contain tandemly repeated zinc finger motifs of the C2-H2 class. All three novel genes were found to be expressed in normal adult human tissues, although the tissue-specific pattern of expression differs markedly. Isolated zinc finger genes were regionally mapped on chromosome 11 using fluorescence in situ suppression hybridization and demonstrated clustering of the genes at 11q13.3-11q13.4 and 11q23.1-11q23.2. Analysis of in situ hybridization to interphase nuclei demonstrated a maximum distance of 1 Mb separating distinct finger genes. This analysis defines two linked multigene families of zinc finger genes to chromosome bands associated with a high frequency of specific translocations associated with malignancies.