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PubMed2003

Correlations between gene expression and gene conservation in fission yeast.

Genes can be expressed at a wide range of levels, and they show different degrees of cross-species conservation. We compared gene expression levels to gene conservation by integrating microarray data from fission yeast (Schizosaccharomyces pombe) with lists of "core" genes (present in worm and budding and fission yeasts), "yeast-specific" genes (present in budding and fission yeasts, but not in worm), and "pombe-specific" genes (present in fission yeast only). Whereas a disproportionate number of core genes are highly expressed in vegetatively growing cells, many pombe-specific genes are expressed at lower levels. This bias is less pronounced in cells undergoing sexual development, when many pombe-specific genes become highly expressed. This implies that organism-specific proteins are more likely to function during specialized processes such as cellular differentiation. Accordingly, pombe-specific genes were overrepresented among genes induced during sexual development; they were particularly enriched in a group of genes induced during meiotic prophase, when homologous chromosomes pair and recombine. This raises the possibility that organism-specific genes with functions in meiotic prophase favor speciation by preventing fruitful meiosis between closely related organisms. Finally, the set of genes induced late during sexual differentiation, at the time of spore formation, was enriched in yeast-specific genes, indicating that these genes play specialized roles in ascospore development.

Conserved Sequence↗
PubMed1993

Conversion of the Salmonella phase 1 flagellin gene fliC to the phase 2 gene fljB on the Escherichia coli K-12 chromosome.

The Escherichia coli-Salmonella typhimurium-Salmonella abortus-equi hybrid strain EJ1420 has the two Salmonella flagellin genes fliC (antigenic determinant i) and fljB (determinant e,n,x) at the same loci as in the Salmonella strains and constitutively expresses the fliC gene because of mutations in the genes mediating phase variation. Selection for motility in semisolid medium containing anti-i flagellum serum yielded 11 motile mutants, which had the active fliC(e,n,x) and silent fljB(e,n,x) genes. Genetic analysis and Southern hybridization indicated that they had mutations only in the fliC gene, not in the fljB gene or the control elements for phase variation. Nucleotide sequence analysis of the fliC(e,n,x) genes from four representative mutants showed that the minimum 38% (565 bp) and maximum 68% (1,013 bp) sequences of the fliC(i) gene are replaced with the corresponding sequences of the fljB(e,n,x) gene. One of the conversion endpoints between the two genes lies somewhere in the 204-bp homologous sequence in the 5' constant region, and the other lies in the short homologous sequence of 6, 8, or 38 bp in the 3' constant region. The conversions include the whole central variable region of the fljB gene, resulting in fliC(e,n,x) genes with the same number of nucleotides (1,503 bp) as the fljB gene. We discuss the mechanisms for gene conversion between the two genes and also some intriguing aspects of flagellar antigenic specificities in various Salmonella serovars from the viewpoint of gene conversion.

Base Sequence↗
PubMed2004

Concurrent expression of latent and a limited number of lytic genes with immune modulation and antiapoptotic function by Kaposi's sarcoma-associated herpesvirus early during infection of primary endothelial and fibroblast cells and subsequent decline of lytic gene expression.

Kaposi's sarcoma-associated herpesvirus (KSHV) infection of in vitro target cells is characterized by the expression of the latency-associated open reading frame (ORF) 73 gene (LANA-1) and the absence of progeny virus production. This default latent infection can be switched into lytic cycle by phorbol ester and by the lytic cycle ORF 50 (RTA) protein. In this study, the kinetics of latent and lytic gene expression immediately following KSHV infection of primary human dermal microvascular endothelial (HMVEC-d) and foreskin fibroblast (HFF) cells were examined by real-time reverse transcriptase PCR and whole-genome array. Within 2 h postinfection (p.i.), high levels of ORF 50 transcripts were detected in both cell types, which declined sharply by 24 h p.i. In contrast, comparatively low levels of ORF 73 expression were detected within 2 h p.i., increased subsequently, were maintained at a steady state, and declined slowly by 120 h p.i. The RTA and LANA-1 proteins were detected in the majority of infected cells by immunoperoxidase assays. In genome array, only 29 of 94 (31%) KSHV genes were expressed, which included 11 immediate-early/early, 8 early, and 5 late lytic genes and 4 latency-associated genes. While the expression of latent ORF 72, 73, and K13 genes continued, nearly all of the lytic genes declined or were undetectable by 8 and 24 h p.i. in HMVEC-d and HFF cells, respectively. Only a limited number of RTA-activated KSHV genes were expressed briefly, and the majority of KSHV genes involved in viral DNA synthesis and structural proteins were not expressed. However, early during infection, the lytic K2, K4, K5, K6, and vIRF2 genes with immune modulation functions and the K7 gene with antiapoptotic function were expressed. Expression of K5 was detected for up to 5 days of observation, and vIRF2 was expressed up to 24 h p.i. The full complement of lytic cycle genes were expressed when 12-O-tetradecanoylphorbol-13-acetate was added to the HMVEC-d cells after 48 h p.i. These data suggest that in contrast to alpha- and betaherpesviruses and some members of gammaherpesviruses, gamma-2 KSHV in vitro infection is characterized by the concurrent expression of latent and a limited number of lytic genes immediately following infection and a subsequent decline and/or absence of lytic gene expression with the persistence of latent genes. Expression of its limited lytic cycle genes could be a "strategy" that evolved in KSHV allowing it to evade the immune system and to provide the necessary factors and time to establish and/or maintain latency during the initial phases of infection. These are unique observations among in vitro herpesvirus infections and may have important implications in KSHV biology and pathogenesis.

Antigens, Viral↗
PubMed1985

gamma 2-Thymidine kinase chimeras are identically transcribed but regulated a gamma 2 genes in herpes simplex virus genomes and as beta genes in cell genomes.

True gamma or gamma 2 genes, unlike alpha, beta, and gamma 1 (beta gamma) genes of herpes simplex virus 1 (HSV-1), stringently require viral DNA synthesis for their expression. We report that gamma 2 genes resident in cells were induced in trans by infection with HSV-1 but that the induction did not require amplification of either the resident gene or the infecting viral genome. Specifically, to test the hypothesis that expression of these genes is amplification dependent, we constructed two sets of gamma 2-thymidine kinase (TK) chimeric genes. The first (pRB3038) consisted of the promoter-regulatory region and a portion of 5'-transcribed noncoding region of the domain of a gamma 2 gene identified by Hall et al. (J. Virol. 43:594-607) in the HSV-1(F) BamHI fragment D' to the 5'-transcribed noncoding and coding regions of the TK gene. The second (pRB3048) contained, in addition, an origin of HSV-1 DNA replication. Cells transfected with either the first or second construct and selected for the TK+ phenotype were then tested for TK induction after superinfection with HSV-1(F) delta 305, containing a deletion in the coding sequences of the TK gene, and viruses containing, in addition, a ts lesion in the alpha 4 regulatory protein (ts502 delta 305) or in the beta 8 major DNA-binding protein (tsHA1 delta 305). The results were as follows: induction by infection with TK- virus of chimeric TK genes with or without an origin of DNA replication was dependent on functional alpha 4 protein but not on viral DNA synthesis; the resident chimeric gene in cells selected for G418 (neomycin) resistance was regulated in the same fashion; the chimeric gene recombined into the viral DNA was regulated as a gamma 2 gene in that its expression in infected cells was dependent on viral DNA synthesis; the gamma 2-chimeric genes resident in the host and in viral genomes were transcribed from the donor BamHI fragment D' containing the promoter-regulatory domain of the gamma 2 gene. The significance of the differential regulation of gamma 2 genes in the environments of host and viral genomes by viral trans-acting factors is discussed.

Animals↗
PubMed2006

Extraocular muscle morphogenesis and gene expression are regulated by Pitx2 gene dose.

PURPOSE: PITX2 gene dose plays a central role in Axenfeld-Rieger syndrome. The purpose of this study was to test the hypothesis that the effects of Pitx2 gene dose on eye development can be molecularly dissected in available Pitx2 mutant mice. METHODS: A panel of mice with Pitx2 gene dose ranging from wild-type (+/+) to none (-/-) was generated. Eye morphogenesis was assessed in animals with each Pitx2 gene dose. We also compared global gene expression in eye primordia taken from e12.5 Pitx2+/+, Pitx2+/-, Pitx2-/- embryos using gene microarrays. The validity of microarray results was confirmed by qRT-PCR. RESULTS: Morphogenesis of all extraocular muscle bundles correlated highly with Pitx2 gene dose, but there were some differences in sensitivity among muscle groups. Superior and inferior oblique muscles were most sensitive and disappeared before the four rectus muscles. Expression of muscle-specific genes was globally sensitive to Pitx2 gene dose, including the muscle-specific transcription factor genes Myf5, Myog, Myod1, Smyd1, Msc, and Csrp3. CONCLUSIONS: Pitx2 gene dose regulates both morphogenesis and gene expression in developing extraocular muscles. The expression of key muscle-specific transcription factor genes is regulated by Pitx2 gene dose, suggesting that sufficient levels of PITX2 protein are essential for early initiation of the myogenic regulatory cascade in extraocular muscles. These results document the first ocular tissue affected by Pitx2 gene dose in a model organism, where the underlying mechanisms can be analyzed, and provide a paradigm for future experiments designed to elucidate additional effects of Pitx2 gene dose during eye development.

Animals↗
PubMed2006

Multiregional gene expression profiling identifies MRPS6 as a possible candidate gene for Parkinson's disease.

Combining large-scale gene expression approaches and bioinformatics may provide insights into the molecular variability of biological processes underlying neurodegeneration. To identify novel candidate genes and mechanisms, we conducted a multiregional gene expression analysis in postmortem brain. Gene arrays were performed utilizing Affymetrix HG U133 Plus 2.0 gene chips. Brain specimens from 21 different brain regions were taken from Parkinson's disease (PD) (n = 22) and normal aged (n = 23) brain donors. The rationale for conducting a multiregional survey of gene expression changes was based on the assumption that if a gene is changed in more than one brain region, it may be a higher probability candidate gene compared to genes that are changed in a single region. Although no gene was significantly changed in all of the 21 brain regions surveyed, we identified 11 candidate genes whose pattern of expression was regulated in at least 18 out of 21 regions. The expression of a gene encoding the mitochondria ribosomal protein S6 (MRPS6) had the highest combined mean fold change and topped the list of regulated genes. The analysis revealed other genes related to apoptosis, cell signaling, and cell cycle that may be of importance to disease pathophysiology. High throughput gene expression is an emerging technology for molecular target discovery in neurological and psychiatric disorders. The top gene reported here is the nuclear encoded MRPS6, a building block of the human mitoribosome of the oxidative phosphorylation system (OXPHOS). Impairments in mitochondrial OXPHOS have been linked to the pathogenesis of PD.

Adult↗
PubMed1987

Primary structure of the Escherichia coli folC gene and its folylpolyglutamate synthetase-dihydrofolate synthetase product and regulation of expression by an upstream gene.

The nucleotide sequence of the gene for folylpoly-gamma-glutamate synthetase-dihydrofolate synthetase (folC) has been determined. The deduced amino acid sequence codes for a protein of Mr 45,380 and contains regions with homology to the A and B regions of ATP-binding sites. The folC gene is adjacent to a gene located 70 base pairs upstream of the initiation codon for folC. The nucleotide sequence of this upstream gene was also determined. Deletion of the upstream gene sequences from recombinant plasmids containing the folC gene results in about a 100-fold decrease in plasmid-dependent folylpolyglutamate synthetase activity, suggesting that the major promoter for folC is 5' to the upstream gene. The upstream gene codes for a protein of Mr 33,346, which is expressed in maxicells and amplified in cells containing the upstream gene in recombinant pUC8 plasmids. Expression of the upstream gene in maxicells was greater than that of folC, as determined by the intensity of 35S-labeled proteins after sodium dodecyl sulfate-gel electrophoresis. A region of dyad symmetry exists between the coding sequences of the two genes which may code for a transcription termination signal and be responsible for the attenuation of the expression of the folC gene relative to the upstream gene. The folC gene is located about 1 kilobase upstream of the purF gene region at 50 min on the Escherichia coli map. The function of the upstream gene product is unknown. It contains sequences with homology to metal-binding domains in nucleic acid-binding proteins. A new purification procedure for obtaining large quantities of folylpolyglutamate synthetase-dihydrofolate synthetase is described.

Amino Acid Sequence↗
PubMed2003

A gene recommender algorithm to identify coexpressed genes in C. elegans.

One of the most important uses of whole-genome expression data is for the discovery of new genes with similar function to a given list of genes (the query) already known to have closely related function. We have developed an algorithm, called the gene recommender, that ranks genes according to how strongly they correlate with a set of query genes in those experiments for which the query genes are most strongly coregulated. We used the gene recommender to find other genes coexpressed with several sets of query genes, including genes known to function in the retinoblastoma complex. Genetic experiments confirmed that one gene (JC8.6) identified by the gene recommender acts with lin-35 Rb to regulate vulval cell fates, and that another gene (wrm-1) acts antagonistically. We find that the gene recommender returns lists of genes with better precision, for fixed levels of recall, than lists generated using the C. elegans expression topomap.

Algorithms↗
PubMed1988

Transcription of genes involved in bacterio-opsin gene expression in mutants of a halophilic archaebacterium.

Recent studies on the regulation of the bacterio-opsin (bop) gene of the archaebacterium Halobacterium halobium suggest that the brp and putative bat genes are involved in bop gene expression or purple membrane assembly. These two genes are located 526 and 1,602 base pairs, respectively, upstream of the bop gene and are both transcribed in the opposite orientation to the bop gene. Transcription of the bop, brp, and putative bat genes was characterized in the wild type, 11 Bop mutants, and a Bop revertant by using a series of RNA probes. Quantitation of the relative mRNA levels for these three genes in the wild type revealed that the brp and bat transcripts are present at approximately 2 and 4%, respectively, of bop mRNA levels under the growth conditions used. Northern (RNA) blot analysis of Bop mutants indicated that insertions in the brp gene affect expression of the putative bat gene. In addition, deletion of most of the bat gene resulted in virtually undetectable levels of bop and brp mRNAs. These and other results lead us to propose that (i) brp gene expression can affect bat gene expression and (ii) the putative bat gene is involved in activating bop and brp gene expression.

Bacteriorhodopsins↗
PubMed1995

Differential expression of the T cell receptor/CD3 genes and their lymphoid-specific transcription factor genes in murine T cell x fibroblast and T cell x B cell hybrids.

We generated cell hybrids between mouse T cell lymphoma EL4 cells and mouse fibroblast B82 cells (BELIII and BELIV) to examine the expression of T cell receptor (TcR)/CD3 genes and their lymphoid-specific transcription factor genes, which are normally detected in EL4 cells. In BELIII and BELIV, expression of the TcR alpha, TcR beta and CD3 delta genes was extinguished, whereas expression of the CD3 epsilon gene was still detected. Expression of the (lymphoid enhancer binding factor 1) LEF-1 gene was extinguished and that of the GATA-3 gene was hardly detected in BELIII and BELIV. Ets-1 gene expression, observed not only in EL4 cells but also in B82 cells, was considerably reduced in BELIII and BELIV. A much higher level of PEBP2 alpha A gene expression was observed in B82 cells than in EL4 cells and was preserved in BELIII and BELIV. To examine whether reduced expression of these genes is also found in T cell x B cell hybrids, we generated an additional cell hybrid between EL4 cells and mouse plasmacytoma S194 cells (SELIII). Marked differences were observed in the expression of the TcR alpha, CD3 delta, LEF-1 and PEBP2 alpha A genes in BEL and SEL hybrids. Expression of the TcR alpha, CD3 delta and LEF-1 genes, which was extinguished in BELIII and BELIV, was detected in SELIII. PEBP2 alpha A gene expression, not detected in S194 cells, was considerably reduced in SELIII. Almost the sum of the chromosomes from the parental cells were retained by, and the presence of every gene was proven, in each cell hybrid. These results suggest that suppression of the expression of lymphoid-specific transcription factor genes may precede that of the TcR/CD3 genes in the cell hybrids, and that the presence of a different trans-acting negative regulatory mechanism(s) suppresses the expression of T cell specific genes in fibroblasts and B cells.

Animals↗
PubMed1995

Gene inactivation in the plant pathogen Glomerella cingulata: three strategies for the disruption of the pectin lyase gene pnlA.

The feasibility of performing routine transformation-mediated mutagenesis in Glomerella cingulata was analysed by adopting three one-step gene disruption strategies targeted at the pectin lyase gene pnlA. The efficiencies of disruption following transformation with gene replacement- or gene truncation-disruption vectors were compared. To effect replacement-disruption, G. cingulata was transformed with a vector carrying DNA from the pnlA locus in which the majority of the coding sequence had been replaced by the gene for hygromycin B resistance. Two of the five transformants investigated contained an inactivated pnlA gene (pnlA-); both also contained ectopically integrated vector sequences. The efficacy of gene disruption by transformation with two gene truncation-disruption vectors was also assessed. Both vectors carried at 5' and 3' truncated copy of the pnlA coding sequence, adjacent to the gene for hygromycin B resistance. The promoter sequences controlling the selectable marker differed in the two vectors. In one vector the homologous G. cingulata gpdA promoter controlled hygromycin B phosphotransferase expression (homologous truncation vector), whereas in the second vector promoter elements were from the Aspergillus nidulans gpdA gene (heterologous truncation vector). Following transformation with the homologous truncation vector, nine transformants were analysed by Southern hybridisation; no transformants contained a disrupted pnlA gene. Of nineteen heterologous truncation vector transformants, three contained a disrupted pnlA gene; Southern analysis revealed single integrations of vector sequence at pnlA in two of these transformants. pnlA mRNA was not detected by Northern hybridisation in pnlA- transformants. pnlA- transformants failed to produce a PNLA protein with a pI identical to one normally detected in wild-type isolates by silver and activity staining of isoelectric focussing gels. Pathogenesis on Capsicum and apple was unaffected by disruption of the pnlA gene, indicating that the corresponding gene product, PNLA, is not essential for pathogenicity. Gene disruption is a feasible method for selectively mutating defined loci in G. cingulata for functional analysis of the corresponding gene products.

Ascomycota↗
PubMed2006

Rate variation as a function of gene origin in plastid-derived genes of peridinin-containing dinoflagellates.

Peridinin-pigmented dinoflagellates contain secondary plastids that seem to have undergone more nearly complete plastid genome reduction than other eukaryotes. Many typically plastid-encoded genes appear to have been transferred to the nucleus, with a few remaining genes found on minicircles. To understand better the evolution of the dinoflagellate plastid, four categories of plastid-associated genes in dinoflagellates were defined based on their history of transfer and evaluated for rate of sequence evolution, including minicircle genes (presumably plastid-encoded), genes probably transferred from the plastid to the nucleus (plastid-transferred), and genes that were likely acquired directly from the nucleus of the previous plastid host (nuclear-transferred). The fourth category, lateral-transferred genes, are plastid-associated genes that do not appear to have a cyanobacterial origin. The evolutionary rates of these gene categories were compared using relative rate tests and likelihood ratio tests. For comparison with other secondary plastid-containing organisms, rates were calculated for the homologous sequences from the haptophyte Emiliania huxleyi. The evolutionary rate of minicircle and plastid-transferred genes in the dinoflagellate was strikingly higher than that of nuclear-transferred and lateral-transferred genes and, also, substantially higher than that of all plastid-associated genes in the haptophyte. Plastid-transferred genes in the dinoflagellate had an accelerated rate of evolution that was variable but, in most cases, not as extreme as the minicircle genes. Furthermore, the nuclear-transferred and lateral-transferred genes showed rates of evolution that are similar to those of other taxa. Thus, nucleus-to-nucleus transferred genes have a more typical rate of sequence evolution, while those whose history was wholly or partially within the dinoflagellate plastid genome have a markedly accelerated rate of evolution.

Animals↗
PubMed2000

The FK520 gene cluster of Streptomyces hygroscopicus var. ascomyceticus (ATCC 14891) contains genes for biosynthesis of unusual polyketide extender units.

FK520 (ascomycin) is a macrolide produced by Streptomyces hygroscopicus var. ascomyceticus (ATCC 14891) that has immunosuppressive, neurotrophic and antifungal activities. To further elucidate the biosynthesis of this and related macrolides, we cloned and sequenced an 80kb region encompassing the FK520 gene cluster. Genes encoding the three polyketide synthase (PKS) subunits (fkbB, fkbC and fkbA), the peptide synthetase (fkbP), the 31-O-methyltransferase (fkbM), the C-9 hydroxylase (fkbD) and the 9-hydroxyl oxidase (fkbO) had the same organization as the genes reported in the FK506 gene cluster of Streptomyces sp. MA6548 (Motamedi, H., Shafiee, A., 1998. The biosynthetic gene cluster for the macrolactone ring of the immunosuppressant FK506. Eur. J. Biochem. 256, 528-534). Disruption of a PKS gene in the cluster using the φC31 phage vector, KC515, led to antibiotic non-producing strains, proving the identity of the cluster. Previous labeling data have indicated that FK520 biosynthesis uses novel polyketide extender units (Byrne, K.M., Shafiee, A., Nielson, J., Arison, B., Monaghan, R.L., Kaplan, L., 1993. The biosynthesis and enzymology of an immunosuppressant, immunomycin, produced by Streptomyces hygroscopicus var, ascomyceticus. Dev. Ind. Microbiol. 32, 29-45). Genes in the flanking regions of the FK520 cluster were identified that appear to be involved in synthesis of these extender units. All but two of these genes were homologous to genes with known function. In addition to a crotonyl-CoA reductase gene (fkbS), at least two other genes are proposed to be involved in biosynthesis of the atypical PKS extender unit ethylmalonyl-CoA, which accounts for the ethyl side chain on C-21 of FK520. A set of five contiguous genes (fkbGHIJK) is proposed to be involved in biosynthesis of an unusual PKS extender unit bearing an oxygen on the alpha-carbon, and leading to the 13- and 15-methoxy side chains. These putative precursor synthesis genes in the flanking regions of the FK520 cluster are not found in the flanking regions of the rapamycin cluster (Molnár, I., Aparicio, J.F., Haydock, S.F., Khaw, L.E., Schwecke, T., König, A., Staunton, J., Leadlay, P.F., 1996. Organisation of the biosynthetic gene cluster for rapamycin in Streptomyces hygroscopicus: analysis of genes flanking the polyketide synthase. Gene 169, 1-7), consistent with labeling data showing that rapamycin biosynthesis uses only malonyl and methylmalonyl extender units.

Acyl Coenzyme A↗
PubMed2000

Characterization of the Fugu rubripes NLK and FN5 genes flanking the NF1 (Neurofibromatosis type 1) gene in the 5' direction and mapping of the human counterparts.

To complete the analysis of the Neurofibromatosis type 1 (NF1) gene region in Fugu rubripes, we characterized the upstream flanking region of the NF1 gene and identified the FN5 (flanking the Fugu NF1 gene in 5' direction) gene and the NLK (Nemo-like kinase) gene as its flanking genes. The FN5 gene spans 3807bp and encompasses four exons, three of which belong to the expanded 5' UTR. Only 11% of the FN5 transcript is protein-coding. The function of the FN5 protein spanning 59 amino acids is unknown. We also characterized the human and the mouse FN5 transcripts and found 85% and 83% similarity of deduced amino acid sequences compared with Fugu. Two copies of the human FN5 gene were identified, one on chromosome 17q21.3-q22 several megabases distal to the NF1 gene at 17q11.2. The second copy of the FN5 gene was mapped to 11q13.3-q23.3. In Fugu, the FN5 gene is flanked by the NLK gene, which spans 4513bp from the translation start to the stop codon and encompasses 11 exons. Comparing the deduced amino acid sequences, 82% overall similarity was observed between Fugu and mouse or human NLK and 67% similarity between the Fugu NLK and the highly related LIT-1 kinase of Caenorhabditis elegans, which has been shown, like the vertebrate counterpart, to be involved in the Wnt signalling pathway. We mapped the human NLK gene to 17q11.2 between markers D17S935 and D17S120, more than 1Mb proximal to the NF1 gene. The characterization of the 5' flanking region presented here, together with that of the 3' region, demonstrates the profound differences between Fugu and human considering the gene content within the region flanking the NF1 gene.

Amino Acid Sequence↗
PubMed1998

Physical linkage of the human growth hormone gene family and the thyroid hormone receptor interacting protein-1 gene on chromosome 17.

A P1 cloned insert of about 85.5 kilobases (kb) was isolated, containing four members of the human growth hormone/chorionic somatomammotropin (GH/CS) gene family and the thyroid hormone receptor interacting protein (TRIP-1) gene. The presence of the CS-like, CS-A, GH-variant and, most downstream, CS-B gene was confirmed by DNA blotting and sequence analysis. The TRIP-1 gene was detected 40 kb downstream of the CS-B gene and in the reverse transcriptional orientation to all the GH/CS genes. The TRIP-1 gene is highly homologous to the SUG-1 gene in yeast and is evolutionarily conserved among several species. Based on the common location of the GH and TRIP-1 (or homologue) genes on the same chromosome in the human, pig and rat genomes, we suggest that these loci are physically linked. Previously, it was reported that a muscle-specific sodium channel (SCN4A) gene is located immediately upstream of the pituitary growth hormone (GH-N) gene, and is linked to the GH gene locus in both humans and rats. This suggests a further linkage between the SCN4A, GH and TRIP-1 loci. Also, deoxyribonuclease hypersensitive sites have been reported in and around these loci and were associated with an important locus control region for the GH/CS genes. Unlike the GH/CS genes, we show, using reverse transcriptase-polymerase chain reaction that the TRIP-1 gene is expressed ubiquitously and, through RNA blotting, as a 1.4-kb transcript. This implies an open and active chromatin structure. The possible effect of this structure on the adjacent human GH/CS gene locus is discussed.

ATPases Associated with Diverse Cellular Activitie↗
PubMed1990

Structure and in vitro transcription of the rat CYP2A1 and CYP2A2 genes and regional localization of the CYP2A gene subfamily on mouse chromosome 7.

The CYP2A1 and CYP2A2 genes code for hepatic steroid hydroxylases and differ in their development regulation and expression in male and female rats. In order to explore the mechanism of regulation of these two genes, both genes were isolated and sequenced, their upstream regions compared, and their promoters transcribed in a cell-free system derived from liver. The CYP2A1 gene was completely sequenced and spanned 12,835 bp. The CYP2A2 gene was sequenced except for 1.5 and 12 kbp in the second and fifth introns, respectively. This gene was about 10 kbp longer than CYP2A1. Both genes possess nine exons that displayed overall 93% nucleotide similarity. DNA 4544 and 5529 bp upstream from the CYP2A1 and CYP2A2 genes, respectively, was also sequenced, and the transcription start sites were determined. Both genes had typical TATA boxes but did not contain CCAAT boxes within -100 bp of their polymerase start sites. CYP2A1, however, contained a reverse CCAAT box between -85 and -90. Search of the Gene Bank revealed a 255 bp region that lies -3 kbp upstream from the transcription start site of CYP2A1 displaying similarity with retrovirus polymerase. Two regions upstream of CYP2A2 were also found that displayed 90% sequence similarity with the consensus long interspersed middle repetitive element (LINE). In addition, an unusual 1.6 kbp inserted sequence was detected between -165 and -1779 bp upstream of the CYP2A2 gene that appears to be a retropseudogene. A nuclear extract derived from adult hepatocytes was used to direct in vitro transcription of the CYP2A1 and CYP2A2 gene promoters. Both genes were accurately transcribed in extracts derived from livers of male and female rats. This result is surprising in view of the fact that the CYP2A1 gene is expressed in adult female rats while the CYP2A2 gene is expressed exclusively in adult males. The CYP2A1 promoter was more actively expressed in both extracts than that of CYP2A2. By analyzing the segregation pattern of CYP2A genes in backcross offspring from an interspecies cross between the laboratory strain NFS/N and the wild mouse Mus musculus musculus, the Cyp2a subfamily was mapped proximal to the Gpi-1 locus near the centromere on chromosome 7.

Amino Acid Sequence↗