NORMAL GENOMIC

• Schweitzer R, Vogan KJ, Tabin CJ
• Similar expression and regulation of Gli2 and Gli3 in the chick limb bud.
• Mech Dev. 2000; 98: 171-4
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• Gli genes encode a family of zinc finger transcription factors that mediate signaling by Hedgehog proteins. We have cloned the chick Gli3 gene and studied its expression in developing chick limbs. Gli3 expression is highly similar to that of chick Gli2. Gli3 mRNA is evenly distributed in the early limb mesenchyme and subsequently downregulated in the posterior mesenchyme by the polarizing activity of Sonic hedgehog. At later stages, Gli3 is expressed in the distal limb mesenchyme.

• Mark C, Abrink M, Hellman L
• Comparative analysis of KRAB zinc finger proteins in rodents and man: evidence for several evolutionarily distinct subfamilies of KRAB zinc finger genes.
• DNA Cell Biol. 1999; 18: 381-96
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• Although the KRAB zinc finger proteins probably constitute the single largest class of transcription factors within the human genome, almost nothing is known about their biological function. To increase our knowledge about this interesting and relatively unexplored family of potent transcriptional repressors, we here present the cloning, structural analysis, and expression study of three novel mouse KRAB zinc finger proteins. In addition, we present an extensive comparative analysis of various members of this gene family based on the structure of the common KRAB A motif. At least three larger subfamilies of KRAB zinc finger proteins are identified: one carrying the classical KRAB A motif only, another holding both a classical KRAB A and a classical KRAB B motif, and a third holding a classical KRAB A and a highly divergent KRAB B domain, named b. A large variation both in size and in primary amino acid sequence was observed in the linker region between the KRAB domain and the C-terminally located zinc finger repeats. This variability indicates that this region is of minor importance for the biological function of KRAB-containing zinc finger proteins. The fact that in many zinc finger genes, the entire or almost the entire linker region is composed of degenerate finger motifs substantiates this conclusion. The absence of identifiable KRAB A and B motifs in the genome of yeast, Saccharomyces cerevisiae, indicates a relatively late appearance of the KRAB domain in evolution and may suggest that the biological functions are restricted to multicellular organisms. In addition, we show that the expression of individual members of one subfamily of KRAB zinc finger genes is restricted to specific hematopoietic cell lineages. This finding suggests that KRAB zinc finger proteins may play a role in lineage commitment, possibly silencing leakage transcription from nonlineage-expressed genes.

• Holmes DI, Wahab NA, Mason RM
• Cloning and characterization of ZNF236, a glucose-regulated Kruppel-like zinc-finger gene mapping to human chromosome 18q22-q23.
• Genomics. 1999; 60: 105-9
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• We report the cDNA cloning and characterization of ZNF236, a novel Kruppel-like zinc-finger gene initially identified by its glucose-regulated expression in human mesangial cells using mRNA differential display. Using the differential display fragment as a probe, we screened a human fetal kidney cDNA library and isolated several clones representing two differently spliced mRNA transcripts, designated ZNF236a and -b. Both transcripts were identical apart from the presence of an additional exon in ZNF236a that truncates the open reading frame. RT-PCR analysis confirmed the expression of both transcripts to be upregulated in human mesangial cells in response to elevated levels of d-glucose. ZNF236a and -b cDNAs encode polypeptides of 174 and 204 kDa, containing 25 and 30 C(2)H(2) zinc-finger motifs, respectively. Northern blot analysis showed that ZNF236 is ubiquitously expressed in all human tissues tested. Expression levels were highest in skeletal muscle and brain, intermediate in heart, pancreas, and placenta, and lowest in kidney, liver, and lung. Southern zoo blot analysis indicated that ZNF236 is conserved in the genomes of all mammalian species tested, but not in yeast. The mapping of ZNF236 to human chromosome 18q22-q23, close to the IDDM6 locus, coupled with the glucose-regulated expression of the gene in human mesangial cells, suggests that ZNF236 may be a candidate gene for diabetic nephropathy.

• Tekki-Kessaris N, Bonventre JV, Boulter CA
• Characterization of the mouse Kid1 gene and identification of a highly related gene, Kid2.
• Gene. 1999; 240: 13-22
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• Kid1 encodes a zinc finger protein that has been implicated in renal cell differentiation. Levels of Kid1 mRNA correlate with maturation of kidney tubule epithelia in rat post-natal kidney development and during kidney regeneration following injury. KID1 is a putative transcriptional repressor, containing a KRAB domain at its amino terminus that mediates transcriptional repression in transient cell transfection assays when fused to a heterologous DNA-binding domain. In this paper, we describe the isolation and characterization of the mouse homologue of Kid1 and the identification of a novel highly related mouse gene, Kid2, Kid1 and Kid2 are tightly linked on mouse chromosome 11 and show conservation across mammals. Both genes are expressed predominantly in the mouse adult kidney and brain, but transcripts are also detected in embryonic brain, kidney, gut and lung, suggesting an additional role for these genes during mouse development.

• Flink IL, Blitz I, Morkin E
• Characterization of cellular nucleic acid binding protein from Xenopus laevis: expression in all three germ layers during early development.
• Dev Dyn. 1998; 211: 123-30
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• The Xenopus CNBP homologue (XCNBP) has been cloned from stage 14 neurula. XCNBP encodes a 18.4-kDa protein containing seven highly conserved zinc finger (Zn-finger) repeats (CX2CX4HX4CX2), with sequence similarity to human, mouse, rat, and yeast CNBP. A unique feature of XCNBP is that it contains a 10 amino acid (aa) deletion in the linker region between Zn-fingers 1 and 2, immediately downstream from an alternatively spliced exon of human CNBP isoforms. A similar deletion is found in mouse and yeast CNBP proteins. The deleted region lacks potential PEST and casein kinase II phosphorylation sites. Because CNBP proteins from a variety of species contain deletions in a similar region, these results suggest that the pattern of alternative processing of CNBP isoforms is highly conserved among metazoa and unicellular eukaryotes. XCNBP RNA is initially maternally derived and is widely expressed throughout early development at the gastrula, neurula, and tailbud stages. At the early gastrula stage, XCNBP is expressed in ectodermal, endodermal, and mesodermal germ layers. Previous data have demonstrated the presence of CNBP in the cytoplasm and nucleus. The interactions of CNBP with single-stranded DNA and RNA suggest that CNBP may serve dual functions in transcriptional and translational regulation in a wide variety of tissues during development.

• Agata Y, Matsuda E, Shimizu A
• Rapid and efficient cloning of cDNAs encoding Kruppel-like zinc finger proteins by degenerate PCR.
• Gene. 1998; 213: 55-64
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• To isolate cDNAs encoding Kruppel-like zinc finger proteins consisting of several hundred members, most of which are yet to be identified, from a limited number of available cells, we developed a rapid and efficient zinc finger gene cloning method based on reverse transcription-polymerase chain reaction (RT-PCR) using tagged, degenerate oligonucleotide primers corresponding to the conserved H/C link followed by the reverse blue selection to identify clones containing properly amplified fragments. More than 5x103 blue colonies were obtained from only 1ng of total RNA. Eighty-eight out of 89 clones, which were randomly picked up from blue colonies and sequenced, encoded 60 different zinc fingers with the expected structure, and among them, only four have been previously described. Furthermore, it was possible to rapidly select clones that were differentially expressed in a tissue and stimulation-specific manner by a differential screening of the zinc-finger cDNA library using probes consisting of distinct sets of the zinc-finger PCR products. These results indicate that our PCR-based method is quite efficient and suitable for analyzing not only zinc finger genes but also other large gene families, especially when the available cells are very limited.

• Cohen ME, Yin M, Paznekas WA, Schertzer M, Wood S, Jabs EW
• Human SLUG gene organization, expression, and chromosome map location on 8q.
• Genomics. 1998; 51: 468-71
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• SLUG is a member of the snail family of zinc finger proteins. It is involved in epithelial to mesenchyme cell transition during neurulation and plays a role in limb bud development. We have isolated and described the human SLUG gene by sequencing a region spanning 4034 bp. The human SLUG gene contains three exons. The SLUG transcript is 2.2 kb and is found in placenta and adult heart, pancreas, liver, kidney, and skeletal muscle, and it codes for a protein of 268 amino acids and 29.989 kDa. This protein contains five zinc finger regions. The human SLUG protein is 95, 93, and 88% homologous to mouse, chicken, and Xenopus slug, respectively, but shows only 47% homology to mouse Snail. The zinc finger region is 100% identical between human and mouse Slug. Slug maps to the long arm of chromosome 8, closely linked to D8S2090 between D8S519 and D8S1098.

• Masu Y, Ikeda S, Okuda-Ashitaka E, Sato E, Ito S
• Expression of murine novel zinc finger proteins highly homologous to Drosophila ovo gene product in testis.
• FEBS Lett. 1998; 421: 224-8
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• We have cloned two isoforms of cDNAs encoding novel zinc finger proteins. One form encodes a 274-amino acid protein containing an acidic amino acid and serine-rich domain and a zinc finger domain which shows high sequence homology to that of Drosophila Ovo protein. The other form encodes a 179-amino acid protein containing only the zinc finger domain. Expression of both proteins possessing an antigenic epitope in COS cells revealed that they are localized in the nucleus. The 1.3-kbp mRNAs are predominantly expressed in testis, and the expression increases from 3 weeks postnatal, implying that these proteins may play important roles in the development of the testes.

• Przyborski SA, Knowles BB, Handel MA, Gurwitch SA, Ackerman SL
• Differential expression of the zinc finger gene Zfp105 during spermatogenesis.
• Mamm Genome. 1998; 9: 758-62
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• We report the isolation of Zfp105, the mouse homolog of the human ZNF35 zinc finger gene. Zfp105 and ZNF35 are highly conserved at the protein and nucleotide level, and Zfp105 maps to a region of mouse Chromosome (Chr) 9 that is homologous to the human region containing ZNF35. Zpf105 is highly expressed in the testis, especially in pachytene spermatocytes and round spermatids. The possible role of this gene product in maintaining an ordered germ cell differentiation process is discussed.

• Ogilvie MK, Hanas JS
• Molecular biology of vertebrate transcription factor IIIA: cloning and characterization of TFIIIA from channel catfish oocytes.
• Gene. 1997; 203: 103-12
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• TFIIIA regulates 5S rRNA synthesis and is the prototype of the Cys2His2 superfamily of zinc finger proteins. Because the TFIIIA aa sequence is highly diverged, elucidating species variation in this factor will yield insights into how zinc fingers bind DNA and how this protein regulates RNAPIII transcription. This study reports the identification, cloning and functional divergence of oocyte TFIIIA from the channel catfish. Catfish oocyte TFIIIA was identified by its association with 5S rRNA in immature ovarian tissue, its molecular weight, and by peptide sequence similarities with Xenopus TFIIIA. The cDNA for this factor was cloned by degenerate PCR and found to code for nine Cys2His2 zinc fingers and a C-terminal tail; only about 40% aa sequence identity was observed with Xenopus TFIIIA. The N-terminal region of catfish TFIIIA contains the oocyte-specific initiating Met amino acid and accompanying conserved residues found in amphibian TFIIIAs but not found in yeast or human TFIIIAs. Catfish TFIIIA lacks the conserved transcription activation domain in its C-terminal tail found in amphibian and human TFIIIA. Catfish TFIIIA was able to bind the catfish and Xenopus 5S RNA genes but did not efficiently promote 5S gene transcription in a rodent RNAPIII transcription system, as did Xenopus TFIIIA. Amino acid conservation in catfish, amphibian, and human TFIIIA zinc fingers allows deduction of possible finger recognition helix alignments along the conserved 5S gene ICRs. For the three N-terminal fingers, this leads to deduction of a compact polypeptide structure with conserved basic residues contacting conserved G nts in the 5S gene C box.

• Lee PL, Gelbart T, West C, Adams M, Blackstone R, Beutler E
• Three genes encoding zinc finger proteins on human chromosome 6p21.3: members of a new subclass of the Kruppel gene family containing the conserved SCAN box domain.
• Genomics. 1997; 43: 191-201
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• Five genes encoding zinc finger proteins of the Cys2His2 (or Kruppel) family were identified by direct cDNA hybridization to YACs 753H12 and 638D7, which encompass a region of human chromosome 6p21.3 extending from just centromeric of the microsatellite marker D6S306 to telomeric of D6S1260. The genes span a distance of approximately 1750 kb. The complete cDNA sequence, genomic structure, and tissue distribution of three of the zinc finger proteins, LD65/ZNF165, ZNF192 (previously called LD5-1), and ZNF193, are described. The three zinc finger proteins do not contain either Kruppel-associated box (KRAB) A or KRAB B domain, present in about one-third of all Kruppel-type zinc finger proteins (E. J. Bellefroid et al., 1991, Proc. Natl. Acad. Sci. USA 88: 3608-3612). The three zinc finger proteins do contain the conserved SCAN box domain (A. J. Williams et al., 1995, J. Biol. Chem. 270: 22143-22152). SCAN boxes are found in eight other genes in the GenBank database, five of which are also in the Kruppel family of zinc finger proteins lacking KRAB A and B domains and thereby define a new subclass of zinc finger proteins. In addition, three polymorphisms were identified in ZNF192, one of the zinc finger proteins. One of the three polymorphisms, Pro163Leu, is the second proline in a proline cluster (PEPP) in a region separating the SCAN box from the zinc finger motifs.

• Omori Y et al.
• Cloning, expression and mapping of a novel human zinc-finger gene TCF17 homologous to rodent Kid1.
• Cytogenet Cell Genet. 1997; 78: 285-8
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• We isolated a novel human zinc-finger gene TCF17 homologous to rat Kid1, a zinc-finger gene of the Kruppel type expressed predominantly in kidney. In the rat this gene seems to be a transcription factor expressed in response to renal injury and ischemia. The 2435-bp human cDNA contained an open reading frame encoding 605 amino acids. The deduced amino acid sequence showed 86.0% and 87.2% identity (91.6% and 92.8% similarity) with the rat Kid1 and mouse Tcf17 respectively. In contrast with rat Kid1, human TCF17 was expressed in all human tissues examined, including kidney. This gene was mapped by FISH to chromosome 5q35.3, where cytogenetic and molecular abnormalities have been reported often in renal cell carcinomas.

• Padanilam BJ, Solursh M
• Identification and localization of a novel zinc finger gene in developing chick skin and feather buds.
• Biochem Biophys Res Commun. 1996; 220: 63-7
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• We have cloned and sequenced a cDNA encoding a novel zinc finger protein (Fzf-1) containing two tandem repeats of zinc finger motifs of the C2H2 type. The cDNA is 3.0 Kb long and has an open reading frame which codes for a protein of 789 amino acids. The expression pattern of the zinc finger gene was studied in chick embryonic skin and feathers by in situ hybridization. The expression of the gene is found to be temporally and spatially regulated. In stage 38 chick embryos, the transcripts are localized to the epidermis but in 10-day-old embryos, the signal is localized to the forming dermis. In 12-day-old chick, the transcripts are localized to the mesenchymal region of the elongated feather buds. Reverse transcription followed by Polymerase Chain Reaction (RT-PCR) did not detect the transcripts in any other tissues.

• Holst C, Zipfel PF
• A zinc finger gene from Onchocerca volvulus encodes a protein with a functional signal peptide and an unusual Ser-His finger motif.
• J Biol Chem. 1996; 271: 16725-33
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• The filarial parasite Onchocerca volvulus is the causative agent of river blindness. In order to identify genes potentially involved in parasite development we cloned a zinc finger-encoding gene from this species. The ovzf-1 gene represents one member of a family of related zinc finger genes. The predicted ovzf-1 translation product of 447 amino acids includes a hydrophobic signal peptide, which is followed by 13 contiguous finger motifs. The domains of fingers II-XIII display several conserved amino acids and a typical Kruppel-like Cys2-His2 motif. The first finger domain has the two conserved Cys residues replaced with Ser residues; however, it includes all additional amino acids typical of zinc finger domains. The N-terminal domain functions as a signal peptide, as it directs secretion of a reporter protein and a truncated Ovzf protein. Expression of an Ovzf protein via the secretory pathway was also confirmed by demonstrating attachment of N-linked carbohydrates to the recombinant protein. Although the recombinant Ovzf protein also includes a signal peptide, immunofluorescence analyses localize it inside a specific compartment of the infected insect cell. Expression of ovzf mRNA is developmentally regulated; no specific transcript is detected in adult female worms but in the infective L3. Identification of a secreted protein that might function in modulating gene expression of host cells provides an interesting tool for the study of parasite-host interaction on a biochemical and molecular level.

• Johnson SW, Lissy NA, Miller PD, Testa JR, Ozols RF, Hamilton TC
• Identification of zinc finger mRNAs using domain-specific differential display.
• Anal Biochem. 1996; 236: 348-52
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• An oligonucleotide primer specific for a conserved amino acid region of the Cys2/His2 zinc finger proteins was used in conjunction with mRNA differential display to amplify related mRNAs from a human ovarian cancer cell line. Six of the 12 cDNAs analyzed from the differential display polyacrylamide gel exhibited zinc finger homology at the nucleotide and predicted amino acid sequence level. None of these cDNA fragments, however, shared complete homology with genes encoding any known zinc finger proteins. All 6 cDNA fragments with zinc finger homology had a poly-A tail and 3 of these fragments contained a putative polyadenylation signal. Northern blot analysis was performed using radiolabeled probes prepared from the 12 cDNA fragments. Two of the 6 cDNA fragments with zinc finger homology hybridized to 3.6- and 6.0-kb mRNAs. In addition, 2 of the fragments which did not contain significant homology to zinc finger or any other known sequences hybridized to 4.1- and 5.8-kb mRNAs. These results suggest that domain-specific differential display may be a useful approach for the identification of novel gene family members as well as for the analysis of changes in gene expression of family members between related cell lines or tissue samples.

• Gebelein B, Mesa K, Urrutia R
• A novel profile of expressed sequence tags for zinc finger encoding genes from the poorly differentiated exocrine pancreatic cell line AR4IP.
• Cancer Lett. 1996; 105: 225-31
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• Genes encoding for C2H2 zinc finger proteins are known to regulate normal cell proliferation and differentiation and have often been found to be mutated in different forms of cancer. We are interested in understanding the role of these genes as regulators of cell proliferation and differentiation in the exocrine pancreas. Therefore, we have generated expressed sequence tags (ESTs) encoding pancreas-enriched zinc finger peptides using the polymerase chain reaction and hybridization techniques [Adams, M.D. et al. (1991) Science, 252, 1651-1656]. Here we report the primary structure and expression pattern of 18 different zinc finger-encoding cDNAs (DZF-1-18) from the azaserine-derived tumoral cell line AR4IP which displays a poorly differentiated phenotype. Sequence analysis shows that all of these clones encode peptides which share the consensus DNA-binding motif with the Drosophila zinc finger transcription factor kruppel. High stringency Northern blot analysis shows that eight different zinc finger transcripts are expressed at high levels in normal adult rat pancreas and therefore constitute good candidates to play a role as transcription factors in exocrine pancreatic cells.

• Bai C, Tolias PP
• Cleavage of RNA hairpins mediated by a developmentally regulated CCCH zinc finger protein.
• Mol Cell Biol. 1996; 16: 6661-7
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• Control of RNA turnover is a major, but poorly understood, aspect of gene regulation. In multicellular organisms, progress toward dissecting RNA turnover pathways has been made by defining some cis-acting sequences that function as either regulatory or cleavage targets (J. G. Belasco and G. Brawerman, Control of Messenger RNA Stability, 1993). However, the identification of genes encoding proteins that regulate or cleave target RNAs has been elusive (C. A. Beelman and R. Parker, Cell 81:79-183, 1995); this gap in knowledge has made it difficult to identify additional components of RNA turnover pathways. We have utilized a modified expression cloning strategy to identify a developmentally regulated gene from Drosophila melanogaster that encodes a RNase that we refer to as Clipper (CLP). Significant sequence matches to open reading frames encoding unknown functions identified from the Caenorhabditis elegans and Saccharomyces cerevisiae genome sequencing projects suggest that all three proteins are members of a new protein family conserved from lower eukaryotes to invertebrates. We demonstrate that a member of this new protein family specifically cleaves RNA hairpins and that this activity resides in a region containing five copies of a previously uncharacterized CCCH zinc finger motif. CLP's endoribonucleolytic activity is distinct from that associated with RNase A (P. Blackburn and S. Moore, p. 317-433, in P. D. Boyer, ed., The Enzymes, vol. XV, part B, 1982) and is unrelated to RNase III processing of rRNAs and tRNAs (J. G. Belasco and G. Brawerman, Control of Messenger RNA Stability, 1993, and S. A. Elela, H. Igel, and M. Ares, Cell 85:115-124, 1995). Our results suggest that CLP may function directly in RNA metabolism.

• Mesa K, Gebelein B, Cook T, Urrutia R
• Identification and characterization of zinc finger encoding genes from the tumoral exocrine pancreatic cell line AR42J.
• Cancer Lett. 1996; 103: 143-9
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• Zinc finger transcription factors are DNA-binding proteins that are known to determine the identity of cells by regulating cell-specific gene expression. In addition, mutations in some members of this family have been found to be associated with several neoplasias, including Wilms' tumor and leukemias. Because the mechanisms that regulate normal, as well as neoplastic, pancreatic cell differentiation are poorly understood, we are searching for pancreas-enriched transcription factors that may determine the identity of pancreatic cells. Towards this end, we have used the polymerase chain reaction and degenerate primers against the highly conserved (Cys2-His2) zinc finger domain to amplify novel transcription factor encoding cDNAs from the well-characterized pancreatic acinar cell line AR42J. Using this approach, we have identified 17 different zinc finger encoding cDNAs (AZF-1 to -17). Sequence analysis shows that all of these clones encode for different zinc finger peptides which share the consensus DNA binding motif with the Drosophila transcription factor kruppel. As a first step in the characterization of these genes, the purified PCR products were used to determine their spatial pattern of expression by northern blot analysis. Using these techniques, we find that numerous zinc finger encoding genes are expressed in AR42J acinar cells as well as in normal adult rat pancreas and suggest that they may play a role as transcription factors in exocrine pancreatic cells.

• Sillard R, Jornvall H, Carlquist M, Mutt V
• Chemical assay for cyst(e)ine-rich peptides detects a novel intestinal peptide ZF-1, homologous to a single zinc-finger motif.
• Eur J Biochem. 1993; 211: 377-80
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• Cysteine is a relatively infrequent constituent of proteins, which in its thiol or half-cystine form contributes in a special manner to their three-dimensional structure. We show that in small cystine-containing peptides, the Cys content is always higher than the average in proteins in general. This observation makes it possible to search for new peptides by monitoring only their Cys content. We have developed a chemical assay for the detection of cyst(e)ine-rich peptides in tissue extracts. Using this assay we have isolated from porcine intestine a novel cysteine-rich peptide, which we denote ZF-1. ZF-1 is homologous to a single zinc-finger motif and has an acetylated N-terminus. This is the first demonstration of the existence of a processed single zinc-finger-like structure. The structural homology of ZF-1 to the zinc-finger motif, present in several metal-binding and DNA-binding proteins, suggests an important role of this peptide in metal transport and/or modulation of gene expression.

• Swalla BJ, Makabe KW, Satoh N, Jeffery WR
• Novel genes expressed differentially in ascidians with alternate modes of development.
• Development. 1993; 119: 307-18
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• We have used a subtractive procedure to isolate cDNA clones encoding genes expressed differentially in ascidian species with alternate modes of development. The ascidians used in this study were Molgula occulta, which develops a tailed (urodele) larva, and Molgula occulta, which develops a tailless (anural) larva. Two of the identified clones, Uro-2 and Uro-11, are described. Southern blots show that the Uro-2 and Uro-11 genes are present in both species, but the corresponding mRNAs are expressed preferentially in the urodele species. In situ hybridization showed that Uro-2 and Uro-11 transcripts accumulate in small oocytes during oogenesis. The maternal Uro-2 and Uro-11 transcripts were distributed throughout the oocyte cytoplasm. Transcript concentrations declined during vitellogenesis, but mature eggs still contain detectable levels of Uro-2 and Uro-11 mRNA. After fertilization, the maternal Uro-2 and Uro-11 transcripts were localized in the ectoplasm of uncleaved zygotes and mostly entered the ectoderm cells during cleavage. The Uro-2 gene appears to produce only maternal transcripts. In contrast, the Uro-11 gene may also produce zygotic transcripts, which accumulate between gastrulation and neurulation in posterior epidermis, neural and tail muscle cells. Zygotic expression of the Uro-11 gene was not detected in embryos of the anural species. The deduced amino acid sequences of the Uro-2 and Uro-11 cDNAs suggest that they encode novel basic proteins with distinctive structural features. The predicted Uro-2 protein contain, a leucine zipper motif, suggesting that it may dimerize with another protein. The predicted Uro-11 protein contains a nuclear localization signal, a region with similarity to part of the DNA-binding motif in the bacterial histone-like HU and IHF proteins, 12 repeats of the proposed DNA-binding motif S(T)PXX, and a potential zinc finger of the C6 or C6H2 class, suggesting that it may be a DNA-binding protein. The Uro-2 and Uro-11 proteins are candidates for regulatory factors involved in the evolutionary transition from urodele to anural development.

• Muller HJ, Skerka C, Bialonski A, Zipfel PF
• Clone pAT 133 identifies a gene that encodes another human member of a class of growth factor-induced genes with almost identical zinc-finger domains.
• Proc Natl Acad Sci U S A. 1991; 88: 10079-83
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• We report the structure and regulation of a gene represented by clone pAT 133, which is induced upon transition from a resting state (G0) through the early phase of the cell cycle (G1). The pAT 133 gene is immediately induced, with FOS-like kinetics, in human T cells and in fibroblasts. Primary structure analysis showed that the encoded protein contains three tandem zinc-finger sequences of the type Cys2-Xaa12-His2. This zinc-finger region, which is thought to bind DNA in a sequence-specific manner, is similar (greater than 80% on the amino acid level) to two previously described transcription factors pAT 225/EGR1 and pAT 591/EGR2. Except for the conserved zinc-finger domains, the amino acid sequences of the three proteins are distinct. This structural similarity suggests that the pAT 133 gene encodes a transcription factor with a specific biological function. Comparing the regulation of these related zinc-finger-encoding genes showed coordinate induction upon mitogenic stimulation of resting T lymphocytes and of resting fibroblasts. However, upon transition from a proliferating (G1) to a resting state of the cell cycle the three genes were differently regulated. In human histiocytic U937 cells mRNA of clone pAT 133 was constitutively expressed, whereas mRNA of pAT 225/EGR1 was induced upon induction of terminal differentiation. In contrast mRNA representing pAT 591/EGR2 was not expressed in these cells. This difference in gene regulation suggests distinct biological roles in the control of cell proliferation for the respective proteins.