NORMAL GENOMIC

• Wang Z, Peters B, Klussmann S, Bender H, Herb A, Krieglstein K
• Gene structure and evolution of Tieg3, a new member of the Tieg family of proteins.
• Gene. 2004; 325: 25-34
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• TGF beta-inducible immediate early gene, Tieg, belongs to the superfamily of Sp1-like transcription factors containing three C(2)H(2)-zinc finger DNA binding motifs close to the C-terminus. So far, Tieg1 and Tieg2 have been identified in human and mouse. We identified Tieg3, a new member of the Tieg protein family by screening a mouse cDNA library. Tieg3 has almost all the known features of the Tieg protein family: it shares a highly conserved C(2)H(2) zinc finger DNA binding domain and is 96% identical to Tieg2 and 86% to Tieg1, respectively. In addition, the three repression domains at the N-terminus, R1, R2 and R3 are conserved in all the Tiegs. Similar to Tieg1 and Tieg2, Tieg3 mRNA is up-regulated in response to TGF beta 1 treatment and can perform the Sp1 sites mediated repression of transcription. A 4 kilobase (kb) long transcript of mouse Tieg3 can be detected using Northern-blot analysis. The gene of mouse Tieg3 contains four exons. Due to the amino acid sequence similarity, mouse Tieg2 is regarded as an orthologue of human Tieg2. However, the mouse Tieg3 gene is localized in a conserved segment on mouse chromosome 12 corresponding to human Tieg2 on chromosome 2 with the same gene order. An interesting explanation for this apparent contradiction might be a homologous recombination leading to loci exchange between the mouse Tieg3 and Tieg2.

• Kudryavtseva EI et al.
• Identification and characterization of Grainyhead-like epithelial transactivator (GET-1), a novel mammalian Grainyhead-like factor.
• Dev Dyn. 2003; 226: 604-17
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• LMO-4 is an LIM-only factor that is highly expressed in many epithelial cells, including those of the epidermis and hair follicles. Because LMOs may function by interacting with DNA-binding proteins, we have used the yeast two-hybrid system to screen mouse skin libraries for LMO-4-interacting DNA-binding proteins. In this screen, we isolated a novel LMO-4-interacting factor highly related to the Drosophila gene Grainyhead. Grainyhead is epidermally expressed and carries out important functions in cuticular formation in the fly embryo. With the identification of this novel mammalian Grainyhead-like gene, referred to as Grainyhead-like epithelial transactivator 1 (GET-1), the known members of the mammalian Grainyhead-like gene family are extended to six, falling into two classes based on sequence homology. Of interest, the expression pattern of GET-1 is similar to that of Drosophila Grainyhead with highest expression in the somatic ectoderm/epidermis, but GET-1 is additionally expressed in epithelial cells of gastrointestinal, genitourinary, and respiratory tracks. The GET-1 protein localizes to the nucleus and binds to at least one Grainyhead DNA-binding site. The GET-1 DNA-binding domain maps to a region containing homology to the Drosophila Grainyhead DNA-binding domain. GET-1 homodimerizes in solution by means of a short C-terminally located domain that is homologous to other Grainyhead-like genes. A short domain located between amino acids 100 and 190, which bears no homology to known transactivation domains, is sufficient to confer transactivation to the heterologous GAL4 DNA-binding domain. In addition, GET-1 appears to contain repression domains consistent with the observation that Grainyhead and other mammalian Grainyhead-like genes can act both as activators and repressors. These data suggest that GET-1 is a transcriptional regulator that may perform important functions in epithelial tissues of mammals.

• Qi H et al.
• AIbZIP, a novel bZIP gene located on chromosome 1q21.3 that is highly expressed in prostate tumors and of which the expression is up-regulated by androgens in LNCaP human prostate cancer cells.
• Cancer Res. 2002; 62: 721-33
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• Androgens play an important role in the development and physiology of the normal prostate as well as in prostate cancer cell proliferation. Comparison of the mRNA expression profiles of control and R1881-treated cultures of LNCaP human prostate cancer cells using cDNA subtraction led to the identification of a novel transcription factor that we named Androgen-Induced bZIP (AIbZIP) protein. AIbZIP is a 395 aa protein with homology to cyclic AMP-responsive element binding protein/activating transcription factor transcription factors. It contains an NH(2)-terminal activation domain, a central bZIP domain, and a COOH-terminal transmembrane domain. The AIbZIP gene is localized on chromosome 1q21.3 and consists of 10 exons. A major 1.7-kb transcript was detected exclusively in the prostate as well as in breast and prostate cancer cell lines. Androgens up-regulate AIbZIP mRNA and protein levels in a dose-dependent manner. The kinetics of AIbZIP mRNA up-regulation and the results of experiments with cycloheximide suggest that AIbZIP may be a delayed response gene. Immunoreactive AIbZIP protein was primarily detected in the cytoplasm of prostatic luminal epithelial cells. Similarly, full-length AIbZIP-green fluorescent protein fusion proteins were localized in the cytoplasm of LNCaP cells, whereas a truncated form of AIbZIP lacking the putative transmembrane domain was exclusively nuclear. Examination of AIbZIP protein and mRNA expression in a series of transurethral resection of the prostate and needle biopsy specimens indicated that AIbZIP is expressed at higher levels in cancerous prostate cells compared with noncancerous prostate cells. The highly tissue-specific expression profile, androgen regulation, chromosomal localization, and expression profile of AIbZIP in prostate tumors suggest that AIbZIP may play an important role in prostate cancer and in androgen receptor signaling in prostate cells. Future studies will confirm a possible relationship between AIbZIP and prostate cancer.

• Qing J, Wei D, Maher VM, McCormick JJ
• Cloning and characterization of a novel gene encoding a putative transmembrane protein with altered expression in some human transformed and tumor-derived cell lines.
• Oncogene. 1999; 18: 335-42
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• Identification and characterization of genes expressed in normal cells and decreased in their malignant counterparts is an important method for detecting candidate tumor suppressors. Using differential display of mRNAs from nontumorigenic infinite life span human fibroblast cell strain MSU-1.1 and an isogenic fibrosarcoma-derived cell line, 6A/SB1, which was derived from chemical carcinogen transformed MSU-1.1 cells, we identified a novel gene, ST7, showing sixfold lower expression in 6A/SB1 cells compared with parental MSU-1.1 cells. Molecular cloning of a near full-length cDNA revealed that the novel gene encodes a putative transmembrane protein composed of 859 amino acids: the 492 N-terminal amino acids including a fivefold cysteine-rich repeat of 40 amino acids homologous to the ligand binding repeat of the known low density lipoprotein receptor, a 24 hydrophobic amino acid stretch spanning the plasma membrane, and a C-terminal domain of 343 residues. ST7 is located on human chromosome 8, band q22.2-23.1, the same locus as the genes involved in acute myeloid leukemia and a locus of high polymorphism in cancer biopsies. The ST7 gene is widely expressed in normal human tissues and is particularly abundant in human heart and skeletal muscle. Northern analysis of 15 tumor cell lines derived from patients and 16 cell lines established from tumors formed in athymic mice by MSU-1.1 cells transformed in culture by various methods showed that 16 of the 31 cell lines have low or undetectable levels of ST7 mRNA. Furthermore, Western blotting analysis using a specific anti-peptide antibody demonstrated that the level of ST7 protein is high in normal fibroblasts and low in 12 sarcoma-derived cell lines tested. Altered expression of ST7 appears to occur at both the transcriptional and post-transcriptional levels. These studies are a first step in characterizing a novel putative receptor protein, whose expression is downregulated in some malignantly transformed cells, and which may play an important role in the transformation process of these cells.

• 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.

• Jin DY, Jeang KT
• Isolation of full-length cDNA and chromosomal localization of human NF-kappaB modulator NEMO to Xq28.
• J Biomed Sci. 1999; 6: 115-20
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• NEMO is an essential component of the IkappaB kinase complex. Others have shown that expression of mouse NEMO can complement the lack of responsiveness to NF-kappaB stimuli in two NEMO-deficient cell lines. Here we report the isolation of a full-length human NEMO cDNA. Virtual translation of human NEMO cDNA predicts a 48-kD coiled-coil protein which shares 87.9% identity and 90.5% similarity with the mouse homolog. By sequence alignment, we mapped the human NEMO gene to chromosome Xq28. We note that the NEMO and the G6PD (glucose-6-phosphate dehydrogenase) loci are arranged in a head-to-head orientation separated by no more than 800 bp. This map location is further supported by the sequence of an alternatively spliced variant of human NEMO mRNA. Thus, human NEMO is an X-linked gene closely adjacent to the G6PD locus.

• Buaas FW, Lee K, Edelhoff S, Disteche C, Braun RE
• Cloning and characterization of the mouse interleukin enhancer binding factor 3 (Ilf3) homolog in a screen for RNA binding proteins.
• Mamm Genome. 1999; 10: 451-6
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• In a screen for RNA-binding proteins expressed during murine spermatogenesis, we have identified a cDNA that encodes a protein of 911 amino acids that contains two copies of the double-stranded RNA-binding motif and has 80% identity with human Interleukin Enhancer Binding Factor 3 (ILF3). Linkage and cytogenetic analyses localized the Ilf3 cDNA to a portion of mouse Chr 9, which shows conserved synteny with a region of human Chr 19 where the human ILF3 gene had been previously localized, supporting that we had cloned the murine homolog of ILF3. Northern analysis indicated the Ilf3 gene is ubiquitously expressed in mouse adult tissues with high levels of expression in the brain, thymus, testis, and ovary. Polyclonal antibodies detected multiple protein species in a subset of the tissues expressing Ilf3 RNA. Immunoreactive species are present at high levels in the thymus, testis, ovary, and the spleen to a lesser extent. The high degree of sequence similarity between the mouse ILF3 protein and other dsRNA binding motif-containing proteins suggests a role in RNA metabolism, while the differential expression indicates the mouse ILF3 protein predominantly functions in tissues containing developing lymphocyte and germ cells.

• Kortschak RD, Reimann H, Zimmer M, Eyre HJ, Saint R, Jenne DE
• The human dead ringer/bright homolog, DRIL1: cDNA cloning, gene structure, and mapping to D19S886, a marker on 19p13.3 that is strictly linked to the Peutz-Jeghers syndrome.
• Genomics. 1998; 51: 288-92
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• The Drosophila gene dead ringer (dri) was isolated as a novel gene encoding a sequence-specific DNA-binding protein. DRI is a founding member of a growing protein family whose members share a conserved DNA binding domain termed the A/T-rich interaction domain. dri is developmentally regulated, being expressed in a restricted set of cells including some neural cells and differentiating cells of the gut and salivary gland ducts. The mouse homolog of dri, bright, has been shown to be expressed in mature B-cells in the immune system, its product trans-activating expression through an IgH enhancer in transient transfection assays. We have cloned a human dri/bright homolog, termed DRIL1. Here we report the exon-intron structure of the gene and show physical linkage within 80 kb to the D19S886 marker on 19p13.3. As this marker is intimately linked to the Peutz-Jeghers syndrome in several large pedigrees, human dri (DRIL1) is a candidate gene for this disorder.

• Aihara T et al.
• Cloning and mapping of SMARCA5 encoding hSNF2H, a novel human homologue of Drosophila ISWI.
• Cytogenet Cell Genet. 1998; 81: 191-3
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• We have isolated a novel cDNA encoding a peptide with 86% sequence homology to hSNF2L protein, a previously isolated human homologue of Drosophila ISWI. This gene, designated SMARCA5, contained an open reading frame of 3,156 nucleotides encoding a 1,052 amino-acid peptide (hSNF2H). As this product also revealed a significant (73%) identity in amino acid sequence to ISWI, a key component of chromatin-remodeling factors in Drosophila, hSNF2H may be another human homologue of this protein and, as such, could be involved in chromatin remodeling in humans. An ATPase domain characteristic of the SWI2/SNF2 family of proteins was highly conserved in ISWI, hSNF2L, and hSNF2H. Northern-blot analysis demonstrated ubiquitous expression of 5.1-kb and 4.1-kb transcripts of the hSNF2H gene. This gene was mapped by FISH to chromosome bands 4q31.1-->q31.2.

• Kasukabe T, Okabe-Kado J, Honma Y
• TRA1, a novel mRNA highly expressed in leukemogenic mouse monocytic sublines but not in nonleukemogenic sublines.
• Blood. 1997; 89: 2975-85
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• Mouse monocytic Mm-A, Mm-P, Mm-S1, and Mm-S2 cells are sublines of mouse monocytic and immortalized Mm-1 cells derived from spontaneously differentiated, mouse myeloblastic M1 cells. Although these subline cells retain their monocytic characteristics in vitro, Mm-A and Mm-P cells are highly leukemogenic to syngeneic SL mice and athymic nude mice, whereas Mm-S1 and Mm-S2 cells are not or are only slightly leukemogenic. To better understand the molecular mechanisms of these levels of leukemogenicity, we investigated putative leukemogenesis-associated genes or oncogenes involved in the maintenance of growth, especially in vivo, by means of differential mRNA display. We isolated a fragment clone (15T01) from Mm-P cells. The mRNA probed with 15T01 was expressed at high levels in leukemogenic Mm-P and Mm-A cells but not in nonleukemogenic Mm-S1 and Mm-S2 cells. The gene corresponding to 15T01, named TRA1, was isolated from an Mm-P cDNA library. The longest open reading frame of the TRA1 clone predicts a peptide containing 204 amino acids with a calculated molecular weight of 23,049 D. The predicted TRA1 protein is cysteine-rich and contains multiple cysteine doublets. A putative normal counterpart gene, named NOR1, was also isolated from a normal mouse kidney cDNA library and sequenced. NOR1 cDNA predicts a peptide containing 234 amino acids. The sequence of 201 amino acids from the C-terminal NOR1 was completely identical to that of TRA1, whereas the remaining N-terminal amino acids (33 amino acids) were longer than that (3 amino acids) of TRA1 and the N-terminus of NOR1 protein contained proline-rich sequence. A similarity search against current nucleotide and protein sequence databases indicated that the NOR1/TRA1 gene(s) is conserved in a wide range of eukaryotes, because apparently homologous genes were identified in Caenorhabditis elegans and Saccharomyces cerevisiae genomes. Northern blotting using TRA1-specific and NOR1-specific probes indicated that TRA1 mRNA is exclusively expressed in leukemogenic but not in nonleukemogenic Mm sublines and normal tissues and also indicated that NOR1 mRNA is expressed in normal tissues, especially in kidney, lung, liver, and bone marrow cells but not in any Mm sublines. After leukemogenic Mm-P cells were induced to differentiate into normal macrophages by sodium butyrate, the normal counterpart, NOR1, was expressed, whereas the TRA1 level decreased. Furthermore, transfection of TRA1 converted nonleukemogenic Mm-S1 cells into leukemogenic cells. These results indicate that the TRA1 gene is associated at least in part with the leukemogenesis of monocytic Mm sublines.

• Fernandes ER, Rooney RJ
• The adenovirus E1A-regulated transcription factor E4F is generated from the human homolog of nuclear factor phiAP3.
• Mol Cell Biol. 1997; 17: 1890-903
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• A 50-kDa cellular factor, E4F, has been implicated in mediating trans activation of the adenovirus E4 gene by the 289R E1A(13S) protein. Previous experiments demonstrated an E1A-dependent increase in E4F DNA binding activity, dependent on phosphorylation, that correlated with the activation of E4 transcription. Using expression screening, we isolated a cDNA clone encoding the E4F protein, as judged by DNA binding characteristics, transcriptional activation, and immunological criteria. The E4F-1 cDNA encodes a 783-amino-acid polypeptide that has 86% sequence identity with the murine nuclear factor phiAP3, a GLI-kruppel-related protein. E4F DNA binding activity is encoded within an amino-terminal region of E4F-1 that contains a zinc finger domain and, as with endogenous E4F, is phosphatase sensitive. We found that E4F was generated from the full-length E4F-1-encoded protein as a 50-kDa amino-terminal fragment. Moreover, E1A(13S) expression induced the phosphorylation of both forms of E4F-1 but differentially regulated their DNA binding activities, stimulating the 50-kDa fragment while reducing the activity of the full-length protein. In transient-transfection assays, the E4F-1 amino-terminal fragment stimulated the adenovirus E4 promoter in the presence of E1A(13S), whereas the full-length protein repressed the promoter in the absence, but not the presence, of E1A. The results indicate that the 50-kDa polypeptide responsible for E4F DNA binding activity is a fragment generated from the human homolog of phiAP3 and that the two forms of the E4F-1 protein are differentially regulated by E1A through phosphorylation.

• Alkema MJ et al.
• MPc2, a new murine homolog of the Drosophila polycomb protein is a member of the mouse polycomb transcriptional repressor complex.
• J Mol Biol. 1997; 273: 993-1003
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• The evolutionarily conserved polycomb and trithorax-group genes are required to maintain stable expression patterns of homeotic genes and other target genes throughout development. Here, we report the cloning and characterization of a novel mouse polycomb homolog, MPc2, in addition to the previously described M33 polycomb gene. Co-immunoprecipitations and subnuclear co-localization studies show that MPc2 interacts with the mouse polycomb-group oncoprotein Bmi1 and is a new member of the mouse polycomb multiprotein complex. Gal4DB-MPc2 or -M33 fusion proteins mediate a five- to tenfold repression of stably integrated reporter constructs carrying GAL4 binding sites, demonstrating that these proteins are transcriptional repressors. The MPc2 gene is localized on chromosome 11, in close proximity to the classical mouse mutations tail short (Ts) and rabo torcido (Rbt). Ts and Rbt hemizygous mice display anemia and transformations of the axial skeleton reminiscent of phenotypes observed in mice with mutated polycomb or trithorax-group genes, suggesting that MPc2 is a candidate gene for Ts and Rbt.

• Ishikawa S et al.
• Isolation and mapping of a human zinc finger gene (ZNF188) homologous to ZNF187, a serum-response-element binding protein.
• Cytogenet Cell Genet. 1997; 77: 185-9
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• From a human pancreas cDNA library we isolated and characterized a novel zinc finger gene encoding a protein homologous to ZNF187, a serum response element-binding protein. The full-length cDNA contained an open reading frame of 1,686 nucleotides encoding a predicted 562-amino-acid peptide that included an ATP-GTP binding site and seven C2H2 zinc finger domains. The consensus sequence of the C2H2 domains (CX2CX3FX5LX2HX3H) is common in the SRE-binding region present in Drosophila Kruppel proteins. An alternatively spliced form of the transcript found in the cDNA library lacked both the ATP-GTP binding site and any C2H2 zinc finger domains. We localized this gene (ZNF188) to chromosome band 7q22.1-->q22.3 by fluorescence in situ hybridization.

• Tymms MJ et al.
• A novel epithelial-expressed ETS gene, ELF3: human and murine cDNA sequences, murine genomic organization, human mapping to 1q32.2 and expression in tissues and cancer.
• Oncogene. 1997; 15: 2449-62
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• The ETS family of genes are implicated in cancers such as Ewings sarcoma, acute myeloid leukemia and chronic myelomonocytic leukemia. Further, they have important functions in embryonic development. Hence, identification and characterization of members of this family are important. We identify a novel ETS family member, ELF3, and report its human and murine cDNA sequences. The mouse cDNA has an alternatively spliced transcript with an extra 60 bp inserted. Hence we present the organization of the murine Elf3 gene together with its exon/intron structure. This gene consists of 9 exons and 8 introns spanning 4.8 kb. ELF3 binds and transactivates ETS sequences and interestingly also shows the ability to bind a GGAT-like purine core, a preferential ETS1/ETS2 type binding site. The expression of ELF3, unlike most other ETS family members, is absent in hematopoietic cells and hematopoietic organs in humans and mice. Intriguingly, the gene is specifically expressed in cell lines of epithelial origin and in organs such as lung, stomach, intestine, kidney that have specialized epithelial cells. We localize the human gene to 1q32.2, a region that is amplified in epithelial tumors of the breast, lung and prostate. Finally, we show that ELF3 expression is increased in a lung carcinoma and adenocarcinoma, as compared to normal tissue. ELF3 is also expressed in cell lines derived from lung cancers. These results suggest that this novel ETS gene may be involved in lung tumorigenesis.

• Yockey CE, Smith G, Izumo S, Shimizu N
• cDNA cloning and characterization of murine transcriptional enhancer factor-1-related protein 1, a transcription factor that binds to the M-CAT motif.
• J Biol Chem. 1996; 271: 3727-36
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• The M-CAT motif is a cis-regulatory DNA sequence that is essential for muscle-specific transcription of several genes. Previously, we had shown that both muscle-specific (A1) and ubiquitous (A2) factors bind to an essential M-CAT motif in the myosin heavy chain beta gene and that the ubiquitous factor is transcriptional enhancer factor (TEF)-1. Here we report the isolation of mouse cDNAs encoding two forms (a and b) of a TEF-1-related protein, TEFR1. The TEFR1a cDNA encodes a 427-amino acid protein. The coding region of TEFR1b is identical to 1a in both nucleotide and predicted amino acid sequence except for the absence of 43 amino acids downstream of the TEA DNA-binding domain. Three TEFR1 transcripts (approximately 7, approximately 3.5, and approximately 2 kilobase pairs) are enriched in differentiated skeletal muscle (myotubes) relative to undifferentiated skeletal muscle (myoblasts) and non-muscle cells in culture. In situ hybridization analysis indicated that TEFR1 transcripts are enriched in the skeletal muscle lineage during mouse embryogenesis. Transient expression of fusion proteins of TEFR1 and the yeast GAL4 DNA-binding domain in cell lines activated the expression of chloramphenicol acetyltransferase (CAT) reporter constructs containing GAL4 binding sites, indicating that TEFR1 contains an activation domain. An anti-TEFR1 polyclonal antibody supershifted the muscle-specific M-CAT.A1 factor complex in gel mobility shift assays, suggesting that TEFR1 is a major component of this complex. Our results suggest that TEFR1 might play a role in the embryonic development of skeletal muscle in the mouse.

• Moffett P, Dayo M, Reece M, McCormick MK, Pelletier J
• Characterization of msim, a murine homologue of the Drosophila sim transcription factor.
• Genomics. 1996; 35: 144-55
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• Mutations in the Drosophila single-minded (sim) gene result in loss of precursor cells that give rise to midline cells of the embryonic central nervous system. During the course of an exon-trapping strategy aimed at identifying transcripts that contribute to the etiology and pathophysiology of Down syndrome, we identified a human exon from the Down syndrome critical region showing significant homology to the Drosophila sim gene. Using a cross-hybridization approach, we have isolated a murine homolog of the Drosophila sim gene, which we designated msim. Nucleotide and predicted amino acid sequence analyses of msim cDNA clones indicate that this gene encodes a member of the basic-helix-loop-helix class of transcription factors. The murine and Drosophila proteins share 88% residues within the basic-helix-loop-helix domain, with an overall homology of 92%. In addition, the N-terminal domain of MSIM contains two PAS dimerization motifs also featured in the Drosophila sim gene product, as well as a small number of other transcription factors. Northern blot analysis of adult murine tissues revealed that the msim gene produces a single mRNA species of approximately 4 kb expressed in a small number of tissues, with the highest levels in the kidneys and lower levels present in skeletal muscle, lung, testis, brain, and heart. In situ hybridization experiments demonstrate that msim is also expressed in early fetal development in the central nervous system and in cartilage primordia. The characteristics of the msim gene are consistent with its putative function as a transcriptional regulator.

• Chiang PW et al.
• Isolation and characterization of the human and mouse homologues (SUPT4H and Supt4h) of the yeast SPT4 gene.
• Genomics. 1996; 34: 368-75
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• To study gene regulation mediated by chromatin in mammals, we isolated the human (SUPT4H) and murine (Supt4h) counterparts of the yeast gene encoding SPT4; the product of this gene presumably interacts with the products of the mammalian homologues (which we have also cloned) of yeast SPT5 and SPT6, thereby modulating chromatin formation and activity. We isolated two different sized human SUPT4H cDNA clones (1464 and 728 nt) and one murine Supt4h (688 nt) cDNA clone; all three encode the same 117-amino-acid protein with conservation of the zinc finger motif found in SPT4. Conservation of this zinc finger motif from yeast to mouse and human implies functional importance. Although the overall sequence homology at the DNA level between the human 728-nt transcript and the murine 688-nt transcript is only 78.4%, the DNA sequence homology is 97.7% within the coding region. At the protein level, the amino acid sequences of the translated murine Supt4h and the human SUPT4H gene products are identical. The likely functional copy of SUPT4H, which has at least two introns, maps to human chromosome 17, with candidate intronless pseudogenes on chromosomes 2, 12, and 20. Buttressing the hypothesis that this is a gene required constitutively, both the human SUPT4H transcripts and the murine Supt4h transcript are expressed widely, although not at equal levels (e.g., such as most histones), in all fetal and adult tissues that we examined.

• Calabi F, Rhodes M, Williamson P, Boyd Y
• Identification and chromosomal mapping of a third mouse runt-like locus.
• Genomics. 1995; 26: 607-10
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• The Drosophila runt gene, which controls early events in embryogenesis, has been shown to have homologues in human and mouse. The human gene on 21q22 is involved in the t(8;21) associated with acute myeloid leukemia. Two mouse runt-like loci encoding DNA-binding proteins have been identified. We report here the isolation and partial sequence of a molecular clone of a third mouse runt-like locus. By using a panel of somatic cell hybrids and interspecific backcross mice, we map the novel locus to the telomeric region of mouse chromosome 4.

• Arakawa H et al.
• Molecular cloning, characterization, and chromosomal mapping of a novel human gene (GTF3A) that is highly homologous to Xenopus transcription factor IIIA.
• Cytogenet Cell Genet. 1995; 70: 235-8
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• We have isolated a novel human cDNA that is highly related to Xenopus transcription factor IIIA (TFIIIA). This clone contains an open reading frame of 1,269 nucleotides encoding 423 amino acids, including nine repeats of the Cys2His2-type of zinc-finger domain. A comparison of its sequence with Xenopus TFIIIA revealed 63% identity in nucleic acids and 58% identity in amino acids over a large portion of the gene and predicted peptide, indicating that the human homologue is likely to function as a transcription factor. The zinc-finger domains of the predicted protein also showed homology with those of human genes such as WT1, transcriptional repressor YY1, and MYC-associated zinc-finger protein (MAZ). Northern analysis showed expression in various tissues examined. The human TFIIIA gene (GTF3A) was localized to chromosome band 13q12.3-->q13.1 by fluorescent in situ hybridization (FISH).

• Sowden J, Morrison K, Schofield J, Putt W, Edwards Y
• A novel cDNA with homology to an RNA polymerase II elongation factor maps to human chromosome 5q31 (TCEB1L) and to mouse chromosome 11 (Tceb1l).
• Genomics. 1995; 29: 145-51
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• Few of the auxiliary factors that assist RNA polymerase II in the process of mRNA chain elongation have been identified. We have isolated a novel cDNA, Tceb1l, from mouse and human sources that encodes a 163-amino-acid protein and shows a significant level of identity with a recently identified RNA polymerase II transcription elongation factor, p15. Tceb1l is highly conserved throughout vertebrates and maps to mouse chromosome 11 and to the syntenic region of human chromosome 5q31. Tceb1l shows a restricted pattern of expression in the early mouse embryo, where it is absent from the neurectoderm; later Tceb1l is expressed in the caudal region of the neural tube, followed by widespread expression in many tissues, including the brain and spinal cord. These observations are consistent with Tceb1l being an RNA polymerase II elongation factor and suggest that Tceb1l/p15-like peptides may be a new family of proteins that influence RNA elongation.

• Li X et al.
• Cloning and chromosomal localization of the human and murine genes for the T-cell transcription factors NFATc and NFATp.
• Cytogenet Cell Genet. 1995; 68: 185-91
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• The nuclear factor of activated T cells (NFAT) is a transcription factor complex involved in the activation of cytokines and cell surface molecules associated with coordinating the actions of different cells required for an immune response. Two different genes have recently been cloned that encode proteins capable of functioning as the pre-existing (p) and cytosolic (c) component of the NFAT transcription complex, NFATc of human and NFATp of murine origin (Northrop et al., 1994; McCaffrey et al., 1993b). We report here the partial cDNA cloning of the murine homolog of NFATc and the human homolog of NFATp, and the chromosomal localization of both genes in both species to conserved syntenic regions. Through the use of mapping panels of human x Chinese hamster and mouse x rodent cells hybrids, the NFATc genes were mapped to human and mouse chromosomes 18. By analyzing a chromosome 18 radiation hybrid panel, the human NFATc gene was localized to the q terminus, closely linked to STS marker D18S497. The murine Nfatc gene was sublocalized to chromosome band 18E4 by FISH. The NFATp genes were mapped by somatic cell hybrid analysis to human chromosome 20 and mouse chromosome 2. Human NFATp was assigned to chromosome region 20q13.2-->q13.3 by FISH. Based on the conserved syntenic region on human chromosome 20 and mouse chromosome 2, murine Nfatp is predicted to reside in the vicinity of a mutant locus wasted. Homozygous wst/wst mice display a phenotype reminiscent of severe combined immune deficiency or ataxia telangiectasia, disorders that could therefore be considered candidates for NFATp mutations.

• Kingsmore SF, Watson ML, Seldin MF
• Genetic mapping of the T lymphocyte-specific transcription factor 7 gene on mouse chromosome 11.
• Mamm Genome. 1995; 6: 378-378

• Yoon JB, Li G, Roeder RG
• Characterization of a family of related cellular transcription factors which can modulate human immunodeficiency virus type 1 transcription in vitro.
• Mol Cell Biol. 1994; 14: 1776-85
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• LBP-1 is a cellular protein which binds strongly to sequences around the human immunodeficiency virus type 1 (HIV-1) initiation site and weakly over the TATA box. We have previously shown that LBP-1 represses HIV-1 transcription by inhibiting the binding of TFIID to the TATA box. Four similar but distinct cDNAs encoding LBP-1 (LBP-1a, -b, -c, and -d) have been isolated. These are products of two related genes, and each gene encodes two alternatively spliced products. Comparison of the amino acid sequence of LBP-1 with entries in the available protein data bases revealed the identity of LBP-1c to alpha-CP2, an alpha-globin transcription factor. These proteins are also homologous to Drosophila melanogaster Elf-1/NTF-1, an essential transcriptional activator that functions during Drosophila embryogenesis. Three of the recombinant LBP-1 isoforms show DNA binding specificity identical to that of native LBP-1 and bind DNA as a multimer. In addition, antisera raised against recombinant LBP-1 recognize native LBP-1 from HeLa nuclear extract. Functional analyses in a cell-free transcription system demonstrate that recombinant LBP-1 specifically represses transcription from a wild-type HIV-1 template but not from an LBP-1 mutant template. Moreover, LBP-1 can function as an activator both in vivo and in vitro, depending on the promoter context. Interestingly, one isoform of LBP-1 which is missing the region of the Elf-1/NTF-1 homology is unable to bind DNA itself and, presumably through heteromer formation, inhibits binding of the other forms of LBP-1, suggesting that it may function as a dominant negative regulator.

• Brugnera E et al.
• Cloning, chromosomal mapping and characterization of the human metal-regulatory transcription factor MTF-1.
• Nucleic Acids Res. 1994; 22: 3167-73
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• Metallothioneins (MTs) are small cysteine-rich proteins that bind heavy metal ions such as zinc, cadmium and copper with high affinity, and have been functionally implicated in heavy metal detoxification and radical scavenging. Transcription of metallothioneins genes is induced by exposure of cells to heavy metals. This induction is mediated by metal-responsive promoter elements (MREs). We have previously cloned the cDNA of an MRE-binding transcription factor (MTF-1) from the mouse. Here we present the human cDNA equivalent of this metal-regulatory factor. Human MTF-1 is a protein of 753 amino acids with 93% amino acid sequence identity to mouse MTF-1 and has an extension of 78 amino acids at the C-terminus without counterpart in the mouse. The factors of both species have the same overall structure including six zinc fingers in the DNA binding domain. We have physically mapped the human MTF-1 gene to human chromosome 1 where it localizes to the short arm in the region 1p32-34, most likely 1p33. Both human and mouse MTF-1 when produced in transfected mammalian cells strongly bind to a consensus MRE of metallothionein promoters. However, human MTF-1 is more effective than the mouse MTF-1 clone in mediating zinc-induced transcription.

• Ohe N et al.
• Chromosomal localization and cDNA sequence of human BTEB, a GC box binding protein.
• Somat Cell Mol Genet. 1993; 19: 499-503
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• Human BTEB cDNA clones have been isolated, sequenced, and the corresponding gene has been assigned to human chromosome 9, region q13, by fluorescent in situ hybridization and DNA blot analysis using DNAs from hybrid cell clones containing a single human chromosome. The cDNA clone encodes a polypeptide of 244 amino acids whose sequence shows a high sequence similarity with the rat BTEB (98% amino acid identity).

• Miyasaka H, Choudhury BK, Hou EW, Li SS
• Molecular cloning and expression of mouse and human cDNA encoding AES and ESG proteins with strong similarity to Drosophila enhancer of split groucho protein.
• Eur J Biochem. 1993; 216: 343-52
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• Mouse and human cDNA encoding AES (amino-terminal enhancer of split) and ESG (enhancer of split groucho) proteins with strong similarity to Drosophila enhancer of split groucho protein were isolated and sequenced. Mouse AES-1 and AES-2 proteins, probably resulting from alternative splicing, contain 202 and 196 amino acids, respectively, while mouse ESG protein consists of 771 amino acids. The amino acid sequences of mouse and human AES proteins were found to exhibit approximately 50% identity to the amino-terminal region of Drosophila groucho, mouse ESG and human transducin-like enhancer of split (TLE) proteins. Mouse AES transcripts of 1.5 kb and 1.2 kb were abundantly expressed in muscle, heart and brain. Human AES transcripts of 1.6 kb and 1.4 kb were predominantly present in muscle, heart and placenta. Mouse ESG (homolog of human TLE 3) transcripts of 3.3 kb and 4.0 kb were found only in testis, while human TLE 1 transcripts of 4.5 kb was more abundant in muscle and placenta compared to heart, brain, lung, liver, kidney and pancreas. Human AES, TLE 1 and TLE 3 genes were mapped to chromosomes 19, 9 and 15, respectively, using human and Chinese hamster hybrid cell lines.