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Acyl-CoA-binding protein (ACBP) is a 10 kDa protein isolated from bovine liver by virtue of its ability to bind and induce the synthesis of medium-chain acyl-CoA esters. Surprisingly, it turned out to be identical to a protein named diazepam-binding Inhibitor (DBI) claimed to be an endogenous modulator of the GABAA receptor in brain membranes. ACBP/DBI, or proteolytically derived polypeptides of ACBP/DBI, have also been implicated in the control of steroidogenesis in mitochondria and glucose-stimulated insulin secretion. Thus, it appears that ACBP/DBI is a remarkable, versatile protein. Now we have molecularly cloned and characterized the ACBP/DBI gene family in rat. The rat ACBP/DBI gene family comprises one expressed gene and four processed pseudogenes of which one was shown to exist in two allelic forms. The expressed gene is organized into four exons and three introns. There is a remarkable correspondence between the structural modules of ACBP/DBI as determined by 1H nuclear magnetic resonance spectroscopy and the exon-intron architecture of the ACBP/DBI gene. Detailed analyses of transcription of the ACBP/DBI gene in brain and liver were performed to map transcription initiation sites and to examine if transcripts from the ACBP/DBI gene were subject to alternative processing. In both brain and liver, transcription is initiated from two major and multiple minor initiation sites. No evidence for alternative splicing was obtained. The promoter region of the ACBP/DBI gene is located in a CpG island and lacks a canonical TATA box. Thus, the ACDB/DBI gene exhibits all the hallmarks of a typical housekeeping gene.
J Mol Biol 1992 Dec 05
PMID:Acyl-CoA-binding protein/diazepam-binding inhibitor gene and pseudogenes. A typical housekeeping gene family. 146 8

Vacuolar class I beta-1,3-glucanases (EC 3.2.1.39) are believed to be important in the induced defense reaction of plants to fungal infection. We used antisense transformation to test this hypothesis and to identify other possible physiological functions of this enzyme. Nicotiana sylvestris plants were transformed with antisense constructions containing the region from position 27 to 608 of the coding sequence of the basic, vacuolar beta-1,3-glucanase gene GLA of tobacco regulated by cauliflower mosaic virus 35S RNA expression signals. Plants homozygous for this transgene showed a marked, ca. 20-fold reduction in the constitutive expression of class I beta-1,3-glucanase antigen in their leaves. RNA blot analysis indicated that the antisense plants expressed low levels of the sense transcript of the host beta-1,3-glucanase gene and the antisense transcript of the transgene. Immune blot analysis of plant extracts indicated that only expression of the N. sylvestris homologue of class I tobacco beta-1,3-glucanase and not the acidic, class II isoforms of the enzyme was blocked in the antisense plants. Class I isoforms of beta-1,3-glucanase and chitinase were coordinately induced in leaves of untransformed and empty-vector-transformed N. sylvestris plants treated with ethylene or infected with the fungal leaf pathogen Cercospora nicotianae. In antisense plants, chitinase but not beta-1,3-glucanase was induced under these conditions indicating that antisense transformation effectively blocks constitutive as well as induced expression of class I beta-1,3-glucanase. Under greenhouse conditions, antisense plants developed normally and were fertile. The plants did not exhibit increased susceptibility to C. nicotianae infection. These results suggest that expression of the beta-1,3-glucanase isoform blocked by antisense transformation is not necessary for 'housekeeping' functions of N. sylvestris nor defense against the fungal pathogen tested.
Plant Mol Biol 1992 Aug
PMID:The function of vacuolar beta-1,3-glucanase investigated by antisense transformation. Susceptibility of transgenic Nicotiana sylvestris plants to Cercospora nicotianae infection. 164 83

A Trypanosoma brucei brucei clone from West Africa was crossed with another T. b. brucei clone from the East African kiboko group. This group is defined by characteristic isoenzyme patterns and kinetoplast DNA maxicircle polymorphisms, and is associated with a wild animal-tsetse transmission cycle. Three types of clone were isolated from the cross, 2 of which were hybrid. The hybrids were heterozygotic at 7 loci where the parents were homozygotic and the hybrids also had molecular karyotypes different from those of both parents. Both molecular karyotypes had an extra non-parental band, which was shown to have a different origin in the 2 sets of clones by Southern analysis with various housekeeping gene probes. This analysis also revealed that although the GPI and PGK genes reside on the same chromosome in parent J10, they are on different chromosomes in parent 196. Hybridisation of PFG blots carrying a variety of other trypanosome stocks confirmed that the GPI gene is not always in the same linkage group as the PGK gene cluster. Given that genetic exchange in trypanosomes involves meiosis, such differences in gene linkage will give rise to progeny with incorrect gene dosage, i.e., certain crosses will be partially infertile. This incipient speciation may explain why natural populations of T. brucei spp. are observed not to be in a randomly mating equilibrium.
Mol Biochem Parasitol 1991 Mar
PMID:Genetic exchange in Trypanosoma brucei brucei: variable chromosomal location of housekeeping genes in different trypanosome stocks. 167 62

A genomic DNA fragment containing the Raf-1 promoter region was isolated by using a cDNA extension clone. Nucleotide sequencing of genomic DNA clones, primer extension, and S1 nuclease assays have been used to identify the 5' ends of Raf-1 RNAs. Consistent with its ubiquitous expression, the Raf-1 promoter region had features of a housekeeping gene in that it was GC-rich (HTF-like), lacked TATA and CAAT boxes, and contained heterogeneous RNA start sites and four potential binding sites for the transcription factor SP1. In addition, an octamer motif (ATTTCAT), a potential binding site for the octamer family of transcription factors, was located at -734 base pairs. The Raf-1 promoter region drove reporter gene expression 30-fold over the promoterless reporter in Cos 7 cells.
Mol Cell Biol 1990 Jul
PMID:Molecular organization of the human Raf-1 promoter region. 169 10

To determine the methylation status of female germ cells in reference to the programmed reversal of X chromosome inactivation in these cells, we examined human fetal ovaries at developmental stages from the time germ cells initiate meiosis to when they cease to synthesize DNA (8-21 weeks gestation). Using methylation-sensitive restriction enzymes, we analyzed 57 MspI sites (32 sites in the CpG islands, and 25 nonclustered sites) from five X-linked housekeeping genes (HPRT, G6PD, P3, PGK, and GLA) and two tissue specific genes (X-linked F9 and autosomal EPO). Methylation patterns were compared to those of male germ cells, sperm, and somatic tissues of both sexes. All 32 MspI sites in CpG islands were unmethylated in germ-cell fractions of fetal ovary and adult testes, which could explain the reversibility of X inactivation in these tissues. However, whereas male meiotic germ cells were extensively methylated outside the islands (in the body of genes) and the methylation patterns resembled those of most somatic tissues, none of the 25 nonclustered CpGs was methylated in DNA contributed by the germ-cell component of fetal ovaries. The presence of faint MspI-like fragments in HpaII digests of fetal testes as well as fetal ovary prior to the onset of meiosis suggests that DNA of primordial germ cells is unmethylated in both sexes. Our observations of meiotic germ cells suggest that the female germ cells remain unmethylated, but that methylation in male germ cells occurs postnatally, prior to or during the early stages of spermatogenesis. In any event, the striking sex difference in methylation status of endogenous single-copy genes in meiotic germ cells could provide a molecular basis for parental imprinting of the mammalian genome.
Somat Cell Mol Genet 1990 May
PMID:Sex difference in methylation of single-copy genes in human meiotic germ cells: implications for X chromosome inactivation, parental imprinting, and origin of CpG mutations. 169 9

Genome exposure studies were carried out on malignant CHO-K1 and C6 rat glioma cells and their respective, phenotypically normal counterparts (reverse-transformed CHO-K1, and both reverse-transformed C6 glioma and normal rat fibroblasts). Cells were subjected to the nick-translation technique previously developed to make visible the exposed (i.e., DNase I-sensitive) nuclear DNA, and examined by both epifluorescence and confocal microscopy. The confocal microscopy, by permitting examination of sections throughout the nucleus, made possible clearer identification of the regions of exposed and sequestered DNA in the cells studied. A peripheral shell of exposed DNA with some discontinuities was displayed in the great majority of the cells with normal phenotype, but in none of the cancer cells. Both types of cells displayed regions of exposed DNA in the nuclear interior, particularly surrounding the nucleoli. In accordance with previous theoretical proposals we postulate: the peripheral nuclear shell of exposed DNA contains differentiation-specific genes that include the specific growth-control genes and that are functional in normal cells but not in cancer; the exposed genes surrounding the nucleoli may represent housekeeping genes active in both normal and cancer cells; and the DNase I-resistant DNA in the interior of the nucleus we postulate to consist for the most part of genes specific to alternative differentiation states and to be sequestered and inactive. Previous differences in evaluation of roles of peripheral and internal DNA sensitivity to DNAse I hydrolysis appear to be reconciled by this formulation. Identification of exposed DNA may be useful in cancer diagnosis.
Somat Cell Mol Genet 1991 Sep
PMID:Confocal microscopy of genome exposure in normal, cancer, and reverse-transformed cells. 172 54

We have identified and characterized a promoter regulatory region for the human insulin-like growth factor-I (IGF-I) gene. The 5'-ends of IGF-I mRNAs were first mapped to a series of sites within a 158-nucleotide portion of exon 1 that was found to be structurally similar to the recently delineated transcription start region of the chicken IGF-I gene. In both species multiple initiation sites are probably a reflection of the absence of typical transcriptional regulatory signals, such as a TATA or CCAAT box, in the proximal promoter, although neither gene sequence resembles a GC-rich housekeeping promoter, which also controls a dispersed initiation region. To test promoter function, hybrid genes were constructed linking human IGF-I DNA to a promoterless reporter plasmid. Fusion genes containing from 385-4300 nucleotides of the IGF-I 5'-flanking region enhanced luciferase activity after transfection into the IGF-I-producing SK-N-MC cell line. A plasmid with 1630 nucleotides of 5'-DNA gave maximal activity and directed accurate initiation of the hybrid gene while the same promoter fragment inserted in the reverse orientation was inert. Although cognate recognition sequences were identified for several transcription factors in the 1630 nucleotides 5' to the transcription start region, no sites were found that resembled the putative GH response element recently mapped to the proximal promoter of the rat Spi2.1 gene.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Endocrinol 1991 Dec
PMID:Structure and function of a human insulin-like growth factor-I gene promoter. 179 41

The calmodulin gene and its flanking sequences from the malaria parasite, Plasmodium falciparum, have been analysed. The structure of this gene is unique amongst other known calmodulin genes. It exists as a single copy on chromosome 14 and has a single intron. The nucleotide sequence of this 4-kb region suggests the existence of three transcriptional units, each separated by a highly A+T-rich sequence. Sequences controlling gene expression might be expected to occur in these intergenic regions. The predicted protein sequences suggest that these other genes are transcribed in different orientations. Primer extension studies suggest that calmodulin mRNA has a major start site 62 bases upstream of the initial ATG. The calmodulin gene possesses consensus eukaryotic TATA, CAAT box, polyadenylation and splice junction sequences. This is the first detailed report of the DNA sequence surrounding a housekeeping gene in P. falciparum.
Mol Biochem Parasitol 1991 May
PMID:The structure of the calmodulin gene of Plasmodium falciparum. 185 74

Phorbol esters selectively and reversibly disassemble the contractile apparatus of cultured skeletal muscle as well as inhibit the synthesis of many contractile proteins without inhibiting that of housekeeping proteins. We now demonstrate that phorbol esters reversibly decrease the mRNA levels of at least six myofibrillar genes: myosin heavy chain, myosin light chain 1/3, myosin light chain 2, cardiac and skeletal alpha-actin, and skeletal troponin T. The steady-state message levels decrease 50- to 100-fold after 48 h of exposure to phorbol esters. These decreases can be attributed at least in part to decreases in transcription rates. For at least two genes, cardiac and skeletal alpha-actin, some of the decreases are the result of increased mRNA turnover. In contrast, the cardiac troponin T steady-state message level does not change, and its transcription rate decreases only transiently upon exposure to phorbol esters. Phorbol esters do not decrease the expression of the housekeeping genes, alpha-tubulin, beta-actin, and gamma-actin. Phorbol esters do not decrease the steady-state message levels of MyoD1, a gene known to be important in the activation of many skeletal muscle-specific genes. Cycloheximide blocks the phorbol ester-induced decreases in transcription, message stability, and the resulting steady-state message level but does not block the tetradecanoyl phorbol acetate-induced rapid disassembly of the I-Z-I complexes. These results suggests a common mechanism for the regulation of many myofibrillar genes independent of MyoD1 mRNA levels, independent of housekeeping genes, but dependent on protein synthesis.
Mol Cell Biol 1991 Sep
PMID:Phorbol esters selectively and reversibly inhibit a subset of myofibrillar genes responsible for the ongoing differentiation program of chick skeletal myotubes. 187 33

The nucleotide sequence of the nod box locus n4 in Rhizobium meliloti was determined and revealed six genes organized in a single transcriptional unit, which are induced in response to a plant signal such as luteolin. Mutations in these genes influence the early steps of nodule development on Medicago, but have no detectable effect on Melilotus, another host for R. meliloti. Based on sequence homology, the first open reading frame (ORF) corresponds to the nodM gene and the last to the nodN gene of Rhizobium leguminosarum. The others do not exhibit similarity to any genes sequenced so far, so we designated them as nolF, nolG, nolH and nolI, respectively. We found that the n4 locus, and especially the nodM and nodN genes, are involved in the production of the root hair deformation (Had) factor. NodM exhibits homology to amidotransferases, primarily to the D-glucosamine synthetase encoded by the glmS gene of Escherichia coli. We demonstrated that in E. coli the regulatory gene nodD together with luteolin can activate nod genes. On this basis we showed that nodM complemented an E. coli glmS- mutation, indicating that nodM can be considered as a glmS gene under plant signal control. Moreover, exogenously supplied D-glucosamine restored nodulation of Medicago by nodM mutants. Our data suggest that in addition to the housekeeping glmS gene of R. melioti, nodM as a second glmS copy provides glucosamine in sufficient amounts for the synthesis of the Had factor.
Mol Gen Genet 1991 Aug
PMID:Six nodulation genes of nod box locus 4 in Rhizobium meliloti are involved in nodulation signal production: nodM codes for D-glucosamine synthetase. 190 18


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