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Although housekeeping functions have been shown for the phosphoenolpyruvate carboxylase (EC 4.1.1.31, PEPC) in plants and in prokaryotes, PEPC is mainly known for its specific role in the primary photosynthetic CO2 fixation in C4 and CAM plants. We have shown that in Sorghum, a monocotyledonous C4 plant, the enzyme is encoded in the nucleus by a small multigene family. Here we report the entire nucleotide sequence (7.5 kb) of the third member (CP21) that completes the structure of the Sorghum PEPC gene family. Nucleotide composition, CpG islands and GC content of the three Sorghum PEPC genes are analysed with respect to their possible implications in the regulation of expression. A study of structure/function and phylogenetic relationships based on the compilation of all PEPC sequences known so far is presented. Data demonstrated that: (1) the different forms of plant PEPC have very similar primary structures, functional and regulatory properties, (2) neither apparent amino acid sequences nor phylogenetic relationships are specific for the C4 and CAM PEPCs and (3) expression of the different genes coding for the Sorghum PEPC isoenzymes is differently regulated (i.e. by light, nitrogen source) in a spatial and temporal manner. These results suggest that the main distinguishing feature between plant PEPCs is to be found at the level of genes expression rather than in their primary structure.
Plant Mol Biol 1993 Feb
PMID:Sorghum phosphoenolpyruvate carboxylase gene family: structure, function and molecular evolution. 844 42

In an attempt to unify the genetic and biological research on Mycobacterium leprae, the aetiological agent of leprosy, a cosmid library was constructed and then ordered by a combination of fingerprinting and hybridization techniques. The genome of M. leprae is represented by four contigs of overlapping clones which, together, account for nearly 2.8Mb of DNA. Several arguments suggest that the gaps between the contigs are small in size and that virtually complete coverage of the chromosome has been obtained. All of the cloned M. leprae genes have been positioned on the contig maps together with the 29 copies of the dispersed repetitive element, RLEP. These have been classified into four groups on the basis of differences in their organization. Several key housekeeping genes were identified and mapped by hybridization with heterologous probes, and the current genome map of this uncultivable pathogen comprises 72 loci.
Mol Microbiol 1993 Jan
PMID:Use of an ordered cosmid library to deduce the genomic organization of Mycobacterium leprae. 844 27

We have cloned and sequenced the nuclear gene of the chloroplast ribosomal protein L21 (rpl21) of Spinacia oleracea. The gene consists of five exons and four introns. All introns are located in the sequence which corresponds to the Escherichia coli-like central core of the protein. L21 mRNA is present in photosynthetic (leaves) and nonphotosynthetic (roots and seeds) plant organs, although large quantitative differences exist. Primer extension and S1 nuclease mapping experiments revealed the existence of two types of transcripts in leaves. The two corresponding start sites were defined as P1 and P2. In roots and seeds, we found only the shorter of the two transcripts (initiated at P2). The nucleotide sequence surrounding P2 resembles promoters for housekeeping and vertebrate r-protein genes. Analysis of several promoter constructions by transient expression confirmed that both transcripts originate from transcription initiation. Results are interpreted to mean that the expression of the rpl21 gene is regulated by alternative promoters. One of the promoters (P2) is constitutive, and the other one (P1) is specifically induced in leaves, i.e., its activation should be related to the transformation of amyloplasts or proplastids to chloroplasts. The gene thus represents the first example of a housekeeping gene which is regulated by the organ-specific usage of alternative promoters. Primer extension analysis and S1 nuclease mapping of another nucleus-encoded chloroplast ribosomal protein gene (rps1) give evidence that the same type of regulation by two-promoter usage might be a more general phenomenon of plant chloroplast-related ribosomal protein genes. Preliminary results indicate that presence of conserved sequences within the rpl21 and rps1 promoter regions which compete for the same DNA binding activities.
Mol Cell Biol 1993 Apr
PMID:Structure and expression of the nuclear gene coding for the chloroplast ribosomal protein L21: developmental regulation of a housekeeping gene by alternative promoters. 845 34

Two types of largest subunit RNA polymerase II (pol II) genes (pol IIA and pol IIB), differing in 3 amino acid substitutions, are encoded in the Trypanosoma brucei (stock 427-60) genome. As a result, the alpha-amanitin-resistant transcription of the procyclic acidic repetitive protein (PARP) and variant surface glycoprotein (VSG) genes was proposed to involve a modified, alpha-amanitin-resistant form of the largest subunit of pol II. Alternatively, pol I could transcribe the PARP and VSG genes. To discriminate between these two models, we deleted the N-terminal domain (about one-third of the polypeptide), which encodes the amino acid substitutions which discriminated the pol IIA and pol IIB genes, at both pol IIB alleles. The pol IIB- trypanosomes still transcribe the PARP genes and the VSG gene promoter region in insect-form trypanosomes by alpha-amanitin-resistant RNA polymerases, while control housekeeping genes are transcribed in an alpha-amanitin-sensitive manner, presumably by pol IIA. We conclude that the alpha-amanitin-resistant transcription of protein coding genes in T. brucei is not mediated by a diverged form of the largest subunit of pol II and that the presence of both the pol IIA and pol IIB genes is not essential for trypanosome viability. This conclusion was further supported by the finding that individual trypanosome variants exhibited allelic heterogeneity for the previously identified amino acid substitutions and that various permutations of the polymorphic amino acids generate at least four different types of largest subunit pol II genes. The expression of the PARP genes and the VSG gene promoter region by alpha-amanitin-resistant RNA polymerases in the pol IIB- trypanosomes provides evidence for transcription of these genes by pol I.
Mol Cell Biol 1993 Jun
PMID:Disruption of largest subunit RNA polymerase II genes in Trypanosoma brucei. 849 77

The mouse Surfeit locus contains an unusually tight cluster of six housekeeping genes (Surf-1 to -6) which are unrelated by sequence homology. Using a mouse Surfeit locus probe, a 16 kb clone has been isolated which contains the human Surf-1 and Surf-3 genes and regions of the human Surf-2 and Surf-5 genes. The organization and juxtaposition of these human Surfeit locus genes are the same as found in the mouse. Using the human clone as a biotinylated probe for fluorescence in situ hybridization (FISH) we have confirmed the location of the human Surfeit locus to chromosome band 9q34. Metaphase spreads of human chronic myeloid leukemic cells containing the t(9;22)(q34;q11) translocation involving The c-abl gene at 9q34.1 an acute nonlymphocytic leukemic cells containing the t(6;9)(q34;p23) translocation involving the can gene at 9q34.1 were analyzed by FISH using the human Surfeit clone as a probe. These analyses locate the human Surfeit locus telomeric to the c-abl and can genes at chromosome band 9q34.1.
Hum Mol Genet 1993 Mar
PMID:The organization and conservation of the human Surfeit gene cluster and its localization telomeric to the c-abl and can proto-oncogenes at chromosome band 9q34.1. 849 13

Small-molecule inhibitors of the housekeeping enzyme farnesyltransferase (FT) suppress the malignant growth of Ras-transformed cells. Previous work suggested that the activity of these compounds reflected effects on actin stress fiber regulation rather than Ras inhibition. Rho proteins regulate stress fiber formation, and one member of this family, RhoB, is farnesylated in vivo. Therefore, we tested the hypothesis that interference with RhoB was the principal basis by which the peptidomimetic FT inhibitor L-739,749 suppressed Ras transformation. The half-life of RhoB was found to be approximately 2 h, supporting the possibility that it could be functionally depleted within the 18-h period required by L-739,749 to induce reversion. Cell treatment with L-739,749 disrupted the vesicular localization of RhoB but did not effect the localization of the closely related RhoA protein. Ras-transformed Rat1 cells ectopically expressing N-myristylated forms of RhoB (Myr-rhoB), whose vesicular localization was unaffected by L-739,749, were resistant to drug treatment. The protective effect of Myr-rhoB required the integrity of the RhoB effector domain and was not due to a gain-of-function effect of myristylation on cell growth. In contrast, Rat1 cells transformed by a myristylated Ras construct remained susceptible to growth inhibition by L-739,749. We concluded that Rho is necessary for Ras transformation and that FT inhibitors suppress the transformed phenotype at least in part by direct or indirect interference with Rho, possibly with RhoB itself.
Mol Cell Biol 1995 Dec
PMID:Evidence that farnesyltransferase inhibitors suppress Ras transformation by interfering with Rho activity. 852 26

Several lines of evidence strongly suggest that DNA methylation is involved in embryo development. Perhaps the most direct evidence comes from experiments with methyltransferase deficient mice. Embryos that express low levels of the maintenance methyltransferase do not develop to term and die at the 5 to 20 somite stage corresponding to the level of the enzyme. In the mouse, dramatic methylation changes have been observed during the early steps of embryo development. Most genes are subject to a process of active demethylation starting promptly after fertilization. Except for a small number of methylated CpG sites in imprinted genes the vast majority of the sites are unmethylated by the stage of cavitation (16 cell). Such genome-wide demethylation may signify an erasure of epigenetic information originating in the highly differentiated gametes. This erasure may be essential for the establishment of a pluripotent state, before specific cell lineages can be determined. The process of laying down a new developmental program involves, initially, global de novo methylation at the stage of pregastrulation followed by gene specific demethylations associated with the onset of activity of these genes. CpG islands characteristic of housekeeping genes, appear to be protected from the global de novo methylation. An exception to this rule is the hypermethylation of CpG islands in X-linked housekeeping genes on the inactive X chromosome and of specific differentially methylated CpG sites in imprinted genes. Primordial germ cells escape the global de novo methylation which takes place at the pregastrula stage and undergo a very similar de novo methylation process in the differentiated gonads (15.5-18.5 days post coitum), forming the methylation patterns which are specific to the gametes. Specific demethylations then form a terminal methylation pattern which is then clonaly inherited in the soma and erased after fertilization.
Hum Mol Genet 1995
PMID:DNA methylation in early development. 854 75

To evaluate the potential for regulation of the insulin receptor substrate IRS-1, we have cloned the mouse IRS-1 gene, identified its promoter, and analyzed promoter activity in the basal state and in response to stimulation. The 5'-region of the mouse IRS-1 gene lacks typical CAAT and TATA boxes but contains nine potential Sp1 binding sites consistent with a housekeeping gene. The 5'-region of the IRS-1 gene also has significant regions of homology with the promoters of the progesterone receptor gene, the insulin-like growth factor I receptor gene, and the androgen receptor gene. Multiple transcription start sites were identified 0.4-1.2 kilobases (kb) upstream from the start codon. Using a chloramphenicol acetyl transferase assay in Chinese hamster ovary (CHO) cells, basal promoter activity was present in the 3.2 kb 5'-flanking region of IRS-1 gene. Within this region, there were 184-base pair and 60-base pair negative regulatory elements at -3.2 kb and -1.6 kb surrounded by positive elements. By gel shift assay, a nuclear factor was identified in CHO cells which binds to -1606 and -1586 sequence in the negative regulatory element and appears to be distinct from C/EBP, CREB, and AP-1. In 3T3-F442A adipocytes dexamethasone treatment significantly decreased IRS-1 mRNA and IRS-1 protein. This was due to a decrease in the half-life of IRS-1 mRNA, with no change in IRS-1 promoter-chloramphenicol acetyl transferase activity. Insulin also decreased IRS-1 protein by approximately 60% within 9 h but did so without altering IRS-1 mRNA levels or chloramphenicol acetyl transferase activity. Thus, both insulin and dexamethasone down-regulate IRS-1 expression at the posttranscriptional level; with insulin this is probably due to an effect on protein half-life, whereas with dexamethasone the effect is due to a change in the half-life of IRS-1 mRNA.
Mol Endocrinol 1995 Oct
PMID:Characterization and regulation of the mouse insulin receptor substrate gene promoter. 854 45

Lateral gene transfer in four strains of Salmonella enterica has been assessed using genomic subtraction. Strain LT2 (subspecies I serovar Typhimurium) chromosomal DNA was used as target and subtracted by three subspecies I strains of serovars Typhimurium (S21), Muenchen (S71), Typhi (M229), and a subspecies V strain (M321). Data from probing random cosmids of LT2 DNA with preparations of the residual LT2 DNA after subtraction were used to estimate the amounts of LT2 DNA not able to hybridize to strains S21, S71, M229, and M321 to be in the range of 84-106, 191-355, 305-629, and 778-1,286 kb, respectively. Several lines of evidence indicate that most of this DNA is from genes not present in strain M321 and not from genes that have diverged in sequence. The amounts correlate with the divergence of the four strains as revealed by multilocus enzyme electrophoresis and sequence variation of housekeeping genes. Sequence of 39 of the fragments from the M321 subtracted residual LT2 DNA revealed only six inserts of known gene function with evidence of both gain and loss of genes during the development of S. enterica clones. Sixteen of the 39 segments have 45% or lower G+C content, below the species average, but over half are within the normal range for the species. We conclude that even within a species, clones may differ by up to 20% of chromosomal DNA, indicating a major role for lateral transfer, and that on the basis of G+C content, a significant proportion of the DNA is from distantly related species.
Mol Biol Evol 1996 Jan
PMID:Gene transfer is a major factor in bacterial evolution. 858 5

A search for genes with sequence homologies to the FMR1 gene resulted in the isolation of mouse and human homologues of the recently described FXR1 gene. The mouse FXR1 gene shares amino acid identity and similarity of 99.1% and 99.6%, respectively, with the human FXR1 gene and amino acid identify and similarity of 67.3% and 79.5% respectively, with the mouse FMR1 gene. The 3' untranslated region of the FXR1 gene is extremely conserved between human and mouse. The gene structure of FXR1 is very similar to that of FMR1 and both genes probably originate from a common ancestral gene. In contrast to the previously published localization, we mapped the transcribed gene to chromosome region 3q28. An intronless form of the FXR1 gene, either processed functional homologue or pseudogene was localized to 12q12. Northern blot analysis of the human FXR1 gene revealed an expression pattern of a housekeeping gene with stronger expression in muscle. RNA in situ hybridization to sections of mouse embryo and adult tissues has shown that during embryonic development the mouse FXR1 mRNA is expressed in different tissues, most prominent in skeletal muscle, the gonads and distinct regions of the central nervous system, and that the expression is restricted to proliferating cells. While FMR1 is highly expressed in proliferating spermatogonia, FXR1 is highly expressed in postmeiotic spermatids.
Hum Mol Genet 1995 Dec
PMID:Highly conserved 3' UTR and expression pattern of FXR1 points to a divergent gene regulation of FXR1 and FMR1. 863 89


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