A Gene for a Novel Zinc-finger Protein Expressed in Differentiated Epithelial Cells and Transiently in Certain Mesenchymal Cells*

We have identified a novel zinc-finger protein whose mRNA is expressed at high levels in the epidermal layer of the skin and in epithelial cells in the tongue, palate, esophagus, stomach, and colon of newborn mice. Expression in epithelial cells is first detected at the time of their differentiation during embryonic development. In addition, during early embryonic development there is expression in mesenchymal cells of the skeletal primordia and the metanephric kidney which is later down-regulated. The expression pattern suggests that the protein could be involved in terminal differentiation of several epithelial cell types and could also be involved in early differentiation of the skeleton and kidney. The carboxyl terminus of the protein contains three zinc fingers with a high degree of homology to erythroid krüppel-like factor and binds to DNA fragments containing CACCC motifs. The amino-terminal portion of the protein is proline and serine-rich and can function as a transcriptional activator. The chromosomal location of the gene was mapped using mouse interspecific backcrosses and was shown to localize to mouse chromosome 4 and to cosegregate with the thioredoxin gene.

[1]  E. L. Green.  Genetics and probability in animal breeding experiments. , 1981 .

[2]  E. L. Green.  Linkage, recombination and mapping , 1981 .

[3]  N. Breslow,et al.  Epidemiological Features of Wilms' Tumor: Results of the National Wilms' Tumor Study , 1982 .

[4]  R. Tjian,et al.  The promoter-specific transcription factor Sp1 binds to upstream sequences in the SV40 early promoter , 1983, Cell.

[5]  D. Bishop.  The information content of phase-known matings for ordering genetic loci. , 1985, Genetic epidemiology.

[6]  Jun Ma,et al.  GAL4-VP16 is an unusually potent transcriptional activator , 1988, Nature.

[7]  M. Seldin,et al.  Genetic analysis of autoimmune gld mice. I. Identification of a restriction fragment length polymorphism closely linked to the gld mutation within a conserved linkage group , 1988, The Journal of experimental medicine.

[8]  D. Wilkinson,et al.  Segment-specific expression of a zinc-finger gene in the developing nervous system of the mouse , 1989, Nature.

[9]  M. Kozak.  The scanning model for translation: an update , 1989, The Journal of cell biology.

[10]  J. Bard,et al.  The candidate Wilms' tumour gene is involved in genitourinary development , 1990, Nature.

[11]  A. Poustka,et al.  Homozygous deletion in Wilms tumours of a zinc-finger gene identified by chromosome jumping , 1990, Nature.

[12]  Michael R. Green,et al.  Evidence for interaction of different eukaryotic transcriptional activators with distinct cellular targets , 1990, Nature.

[13]  D. Housman,et al.  Isolation and characterization of a zinc finger polypeptide gene at the human chromosome 11 Wilms' tumor locus , 1990, Cell.

[14]  J. Saffer,et al.  Developmental expression of Sp1 in the mouse , 1991, Molecular and cellular biology.

[15]  J. Leonard,et al.  Variable role of the long terminal repeat Sp1-binding sites in human immunodeficiency virus replication in T lymphocytes , 1991, Journal of virology.

[16]  M. Greene,et al.  Developmental defects in gorlin syndrome related to a putative tumor suppressor gene on chromosome 9 , 1992, Cell.

[17]  L. Sankaran.  A simple quantitative assay for chloramphenicol acetyltransferase by direct extraction of the labeled product into scintillation cocktail. , 1992, Analytical biochemistry.

[18]  H. Zoghbi,et al.  Identification of a putative gamma-aminobutyric acid (GABA) receptor subunit rho2 cDNA and colocalization of the genes encoding rho2 (GABRR2) and rho1 (GABRR1) to human chromosome 6q14-q21 and mouse chromosome 4. , 1992, Genomics.

[19]  T. Gibson,et al.  Zinc finger-DNA recognition: analysis of base specificity by site-directed mutagenesis. , 1992, Nucleic acids research.

[20]  Y. Fujii‐Kuriyama,et al.  Two regulatory proteins that bind to the basic transcription element (BTE), a GC box sequence in the promoter region of the rat P‐4501A1 gene. , 1992, The EMBO journal.

[21]  B. de Crombrugghe,et al.  Cartilage homeoprotein 1, a homeoprotein selectively expressed in chondrocytes. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[22]  P. Swiatek,et al.  Perinatal lethality and defects in hindbrain development in mice homozygous for a targeted mutation of the zinc finger gene Krox20. , 1993, Genes & development.

[23]  N. Carter,et al.  Multiple self–healing squamous epitheliomata (ESS1) mapped to chromosome 9q22–q31 in families with common ancestry , 1993, Nature Genetics.

[24]  S. Schneider-Maunoury,et al.  Disruption of Krox-20 results in alteration of rhombomeres 3 and 5 in the developing hindbrain , 1993, Cell.

[25]  V. Sukhatme,et al.  A novel repression module, an extensive activation domain, and a bipartite nuclear localization signal defined in the immediate-early transcription factor Egr-1 , 1993, Molecular and cellular biology.

[26]  J. Bieker,et al.  A novel, erythroid cell-specific murine transcription factor that binds to the CACCC element and is related to the Krüppel family of nuclear proteins , 1993, Molecular and cellular biology.

[27]  David Housman,et al.  WT-1 is required for early kidney development , 1993, Cell.

[28]  S. Schneider-Maunoury,et al.  Krox-20 controls myelination in the peripheral nervous system , 1994, Nature.

[29]  M. Seldin,et al.  Mouse thioredoxin gene maps on chromosome 4, whereas its pseudogene maps on chromosome 1. , 1994, Genomics.

[30]  A. Balmain,et al.  An allelotype of squamous carcinoma of the head and neck using microsatellite markers. , 1994, Cancer research.

[31]  Y. Nakamura,et al.  Difference of allelotype between squamous cell carcinoma and adenocarcinoma of the lung. , 1994, Cancer research.

[32]  S. Orkin,et al.  Lethal β-thalassaemia in mice lacking the erythroid CACCC-transcription factor EKLF , 1995, Nature.

[33]  H. Lehrach,et al.  Thioredoxin, a mediator of growth inhibition, maps to 9q31. , 1995, Genomics.

[34]  F. Grosveld,et al.  Defective haematopoiesis in fetal liver resulting from inactivation of the EKLF gene , 1995, Nature.

[35]  R. Myers,et al.  Human Homolog of patched, a Candidate Gene for the Basal Cell Nevus Syndrome , 1996, Science.

[36]  Michael Dean,et al.  Mutations of the Human Homolog of Drosophila patched in the Nevoid Basal Cell Carcinoma Syndrome , 1996, Cell.

[37]  R. Cancedda,et al.  Defective bone formation in Krox-20 mutant mice. , 1996, Development.

[38]  B. de Crombrugghe,et al.  Evidence for three major transcription activation elements in the proximal mouse proalpha2(I) collagen promoter. , 1996, Nucleic acids research.