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At least 901 records · Page 50Linked to original sources
PubMed2004

Newly isolated Bacillus clausii GMBAE 42: an alkaline protease producer capable to grow under higly alkaline conditions.

AIMS: The isolation and identification of new Bacillus sp. capable of growing under highly alkaline conditions as alkaline protease producers. METHODS AND RESULTS: A Bacillus strain capable of growing under highly alkaline conditions was isolated from compost. The strain is a Gram-positive, spore-forming, motile, aerobic, catalase- and oxidase-positive, alkaliphilic bacterium and designated as GMBAE 42. Good growth of the strain was observed at pH 10. The strain was identified as Bacillus clausii according to the physiological properties, cellular fatty acid composition, G + C content of genomic DNA and 16S rRNA gene sequence analyses. The result of 16S rRNA sequence analyses placed this bacterium in a cluster with B. clausii. The G + C content of the genomic DNA of the isolate GMBAE 42 was found to be 49 mol%. The crude extracellular alkaline protease produced by the isolate showed maximal activity at pH 11.0 and 60 degrees C. CONCLUSIONS: The results suggest that isolated strain GMBAE 42 is a new type of B. clausii capable of growing at pH 10.0 and produce extracellular alkaline protease very active at pH 11.0. SIGNIFICANCE AND IMPACT OF THE STUDY: Isolated strain could be used in commercial alkaline protease production and its enzyme can be considered as a candidate as an additive for commercial detergents.

Bacillus↗
PubMed2001

Overlapping sense and antisense transcription units in Trypanosoma brucei.

Procyclins are the major surface glycoproteins of insect-form Trypanosoma brucei. The procyclin expression sites are polycistronic and are transcribed by an alpha-amanitin-resistant polymerase, probably RNA polymerase I (Pol I). The expression sites are flanked by transcription units that are sensitive to alpha-amanitin, which is a hallmark of Pol II-driven transcription. We have analysed a region of 9.5 kb connecting the EP/PAG2 expression site with the downstream transcription unit. The procyclin expression site is longer than was previously realized and contains an additional gene, procyclin-associated gene 4 (PAG4), and a region of unknown function, the T region, that gives rise to trans-spliced, polyadenylated RNAs containing small open reading frames (ORFs). Two new genes, GU1 and GU2, were identified in the downstream transcription unit on the opposite strand. Unexpectedly, the 3' untranslated region of GU2 and the complementary T transcripts overlap by several hundred base pairs. Replacement of GU2 by a unique tag confirmed that sense and antisense transcription occurred from a single chromosomal locus. Overlapping transcription is stage specific and may extend > or = 10 kb in insect-form trypanosomes. The nucleotide composition of the T. brucei genome is such that antisense ORFs occur frequently. If stable mRNAs can be derived from both strands, the coding potential of the genome may be substantially larger than has previously been suspected.

3' Untranslated Regions↗
PubMed1980

Intracisternal A-particle genes: identification in the genome of Mus musculus and comparison of multiple isolates from a mouse gene library.

The genome of Mus musculus contains multiple copies (500 -1000) of DNA sequences related to the 35S RNA of intracisternal type A particles (IAPs). Using labeled IAP RNA as a probe in blot-hybridization experiments, we have identified a characteristic electrophoretic pattern of reactive fragments generated by restriction endonuclease cleavage of mouse DNA. From the genomic blots, we deduced a composite restriction map for a 6.5- to 7-kilobase (kb) DNA region containing sequences homologous to the IAP RNA. Units of this type appeared to be interspersed without obvious regularity in nonhomologous flanking regions. A 5.2-kb segment of this unit was inserted directly into plasmid pBR322 from HindIII/EcoRI digest of mouse DNA. The fragment was cloned and then labeled by nick-translation and used to scan a mouse embryo gene library (average 16-kb inserts in lambda Charon 4A); 1% of the library samples hybridized, confirming the extensive reiteration of IAP genetic units. Among six different library isolates containing 6.5- to 7-kb IAP units, some restriction sites were highly conserved whereas others varied in both occurrence and position. Despite this variation, heteroduplexes between the individual isolates showed continuous IAP homology regions of 7 kb. No flanking region homologies were seen in this limited sample. Some evidence suggests that mouse DNA may contain other dispersed sequence elements related to but smaller than the genetic unit defined above.

Animals↗
PubMed2005

An evolving view of the eukaryotic oligosaccharyltransferase.

Asparagine-linked glycosylation (ALG) is one of the most common protein modification reactions in eukaryotic cells, as many proteins that are translocated across or integrated into the rough endoplasmic reticulum (RER) carry N-linked oligosaccharides. Although the primary focus of this review will be the structure and function of the eukaryotic oligosaccharyltransferase (OST), key findings provided by the analysis of the archaebacterial and eubacterial OST homologues will be reviewed, particularly those that provide insight into the recognition of donor and acceptor substrates. Selection of the fully assembled donor substrate will be considered in the context of the family of human diseases known as congenital disorders of glycosylation (CDG). The yeast and vertebrate OST are surprisingly complex hetero-oligomeric proteins consisting of seven or eight subunits (Ost1p, Ost2p, Ost3p/Ost6p, Ost4p, Ost5p, Stt3p, Wbp1p, and Swp1p in yeast; ribophorin I, DAD1, N33/IAP, OST4, STT3A/STT3B, Ost48, and ribophorin II in mammals). Recent findings from several laboratories have provided overwhelming evidence that the STT3 subunit is critical for catalytic activity. Here, we will consider the evolution and assembly of the eukaryotic OST in light of recent genomic evidence concerning the subunit composition of the enzyme in diverse eukaryotes.

Animals↗
PubMed1987

Nonrandom distribution of MMTV proviral sequences in the mouse genome.

Integrated sequences of mouse mammary tumor virus (MMTV) have been localized in the genomes of five inbred mouse strains (Balb/c, C3H, DBA/2, A.TH, 129-SV) and one mammary tumor cell line (GR). Two major classes of MMTV sequences have been detected in mouse DNA fractions as obtained by Cs2SO4/BAMD (3,6-bis-(acetatomercurimethyl)dioxane) density gradient centrifugation. The first one corresponds to previously described endogenous sequences (Mtv loci), whereas the second one corresponds to endogenous sequences not previously known, and/or recently acquired; in the case of GR cells exogenous sequences may also be present in this class. The genome distribution is somewhat different for the two classes of sequences, the first one being practically only present in the lightest DNA segments of the mouse genome (GC congruent to 38%); the second one being also represented in heavier segments (GC congruent to 43%). This integration pattern suggests that "ancient" endogenous sequences are practically only localized in genome segments of roughly matching composition, whereas exogenous and recently acquired endogenous MMTV sequences may also be present in heavier fractions.

Animals↗
PubMed2026

Multi-sampling allows intra-tumoral heterogeneity querying and vulnerability profiling in glioblastoma.

BACKGROUND: Glioblastoma (GBM) remains a devastating cancer with limited treatment options, largely due to its heterogeneity. While supramaximal resection has recently provided survival benefits, therapeutic profiling of different tumor compartments, particularly its infiltrative edge remains largely unexplored. METHODS: Here, we leveraged magnetic resonance imaging (MRI)-guided multi-sampling, collecting 2 cores and 2 margins per case, to query GBM heterogeneity. Whole-exome and RNA-seq with drug testing in two patient-derived 3D models were used to reveal similarities and differences in genomic and transcriptomic makeups, cellular compositions, and drug responses across cores and margins. Bioinformatics interrogations further identified response biomarkers. RESULTS: Mutation analysis showed that oncogenes exhibited a higher degree of spatial heterogeneity than tumor suppressor genes, regardless of MRI status. While the mesenchymal transcriptional subtype with extracellular matrix remodeling, stress response, and immune programs were preferentially enriched in enhancing cores, proneural tumors with neurological processes favored non-enhancing margins. Using a 15-drug GBM-targeted panel, ERK (ulixertinib) and PI3K pathway (paxalisib, CC-115) inhibitors showed preferential efficacy in enhancing cores and non-enhancing margins, respectively. The anti-apoptosis, pan-Bcl2 agent navitoclax and the epigenetic drug trotabresib represented the most effective, tumor-wide monotherapies. Importantly, drug combinations generally outperformed single agents across all regions. CONCLUSIONS: This work demonstrates the regional heterogeneity of therapeutic vulnerabilities in GBM ex vivo, showing various drugs with tumor-wide or MRI-enhancement informed activity. These findings offer preclinical bases of numerous monotherapies and drug combinations for future clinical trial design.

Humans↗
PubMed2026

Metabolism pathway-based subtyping in pancreatic adenocarcinoma: an integrated study by bulk RNA-sequence and machine learning algorithms.

BACKGROUND: Pancreatic adenocarcinoma (PAAD) is highly aggressive, and its tumor microenvironment has significant metabolic and immune microenvironment complexity and genomic instability. In this study, by integrating the metabolic pathway activity score and clinical data, we constructed a novel risk assessment model to reveal the unique biological behavior and clinical significance behind different PAAD subtypes. METHODS: In this study, the transcriptome and clinical data of TCGA and GSE57495 databases were integrated to explore the interaction between metabolic pathways. Based on unsupervised clustering analysis of pathway activity and survival prognosis, patients with PAAD were classified into metabolic subtypes with significant prognostic differences. Subsequently, we assessed the heterogeneity of these subtypes in terms of clinical outcomes, genomic characteristics, and immune microenvironment composition. Based on the differentially expressed genes (DEGs) among metabolic subtypes, a clinical prognostic risk model and nomogram were constructed, which were double-validated by GSE57495-independent cohort and GSE57495 + TCGA-PAAD combined cohort. Finally, the correlations between risk scores (RSs) and signaling pathway activity and tumor immune microenvironment characteristics were evaluated. RESULTS: Based on metabolic pathway correlation and prognostic information, 240 patients in the TCGA-PAAD and GSE57495 datasets were divided into three subgroups. There were significant differences between subgroups in gene expression, pathway activity, clinical prognosis, and immune infiltration characteristics among the subtypes. Using machine learning algorithms, an RS model was constructed from DEGs among the subgroups, with the random forest method showing the best performance. A nomogram integrating the RS and clinical indicators demonstrated excellent predictive accuracy for 1-, 3-, and 5-year survival rates, confirming the RS as an independent prognostic factor. High- and low-risk groups exhibited significant differences in immune infiltration, pathway activity, and gene mutations. Drug sensitivity analysis showed that the high-risk group was more sensitive to AZD6244, ABT737, and other drugs. CONCLUSION: This study stratified patients with PAAD into three subgroups based on metabolic pathways and prognostic information, revealing significant differences in clinical outcomes, immune characteristics, and genetic mutations. The robust RS model developed from these findings demonstrated strong predictive power for patient survival and identified promising therapeutic strategies, providing valuable insights for advancing precision medicine in PAAD.

immune microenvironment↗
PubMed2003

Functional divergence of a syntenic invertase gene family in tomato, potato, and Arabidopsis.

Comparative analysis of complex developmental pathways depends on our ability to resolve the function of members of gene families across taxonomic groups. LIN5, which belongs to a small gene family of apoplastic invertases in tomato (Lycopersicon esculentum), is a quantitative trait locus that modifies fruit sugar composition. We have compared the genomic organization and expression of this gene family in the two distantly related species: tomato and Arabidopsis. Invertase family members reside on segmental duplications in the near-colinear genomes of tomato and potato (Solanum tuberosum). These chromosomal segments are syntenically duplicated in the model plant Arabidopsis. On the basis of phylogenetic analysis of genes in the microsyntenic region, we conclude that these segmental duplications arose independently after the separation of the tomato/potato clade from Arabidopsis. Rapid regulatory divergence is characteristic of the invertase family. Interestingly, although the processes of gene duplication and specialization of expression occurred separately in the two species, synteny-based orthologs from both clades acquired similar organ-specific expression. This similar expression pattern of the genes is evidence of comparable evolutionary constraints (parallel evolution) rather than of functional orthology. The observation that functional orthology cannot be identified through analysis of expression similarity highlights the caution that needs to be exercised in extrapolating developmental networks from a model organism.

Arabidopsis↗
PubMed2003

Characterization of Staphylococcus aureus SarA binding sites.

The staphylococcal accessory regulator locus (sarA) encodes a DNA-binding protein (SarA) that modulates expression of over 100 genes. Whether this occurs via a direct interaction between SarA and cis elements associated with its target genes is unclear, partly because the definitive characteristics of a SarA binding site have not been identified. In this work, electrophoretic mobility shift assays (EMSAs) were used to identify a SarA binding site(s) upstream of the SarA-regulated gene cna. The results suggest the existence of multiple high-affinity binding sites within the cna promoter region. Using a SELEX (systematic evolution of ligands by exponential enrichment) procedure and purified, recombinant SarA, we also selected DNA targets that contain a high-affinity SarA binding site from a random pool of DNA fragments. These fragments were subsequently cloned and sequenced. Randomly chosen clones were also examined by EMSA. These DNA fragments bound SarA with affinities comparable to those of recognized SarA-regulated genes, including cna, fnbA, and sspA. The composition of SarA-selected DNAs was AT rich, which is consistent with the nucleotide composition of the Staphylococcus aureus genome. Alignment of selected DNAs revealed a 7-bp consensus (ATTTTAT) that was present with no more than one mismatch in 46 of 56 sequenced clones. By using the same criteria, consensus binding sites were also identified upstream of the S. aureus genes spa, fnbA, sspA, agr, hla, and cna. With the exception of cna, which has not been previously examined, this 7-bp motif was within the putative SarA binding site previously associated with each gene.

Adhesins, Bacterial↗
PubMed2004

Structural protein requirements in equine arteritis virus assembly.

Equine arteritis virus (EAV) is an enveloped, positive-stranded RNA virus belonging to the family Arteriviridae of the order Nidovirales. EAV particles contain seven structural proteins: the nucleocapsid protein N, the unglycosylated envelope proteins M and E, and the N-glycosylated membrane proteins GP(2b) (previously named G(S)), GP(3), GP(4), and GP(5) (previously named G(L)). Proteins N, M, and GP(5) are major virion components, E occurs in virus particles in intermediate amounts, and GP(4), GP(3), and GP(2b) are minor structural proteins. The M and GP(5) proteins occur in virus particles as disulfide-linked heterodimers while the GP(4), GP(3), and GP(2b) proteins are incorporated into virions as a heterotrimeric complex. Here, we studied the effect on virus assembly of inactivating the structural protein genes one by one in the context of a (full-length) EAV cDNA clone. It appeared that the three major structural proteins are essential for particle formation, while the other four virion proteins are dispensable. When one of the GP(2b), GP(3), or GP(4) proteins was missing, the incorporation of the remaining two minor envelope glycoproteins was completely blocked while that of the E protein was greatly reduced. The absence of E entirely prevented the incorporation of the GP(2b), GP(3), and GP(4) proteins into viral particles. EAV particles lacking GP(2b), GP(3), GP(4), and E did not markedly differ from wild-type virions in buoyant density, major structural protein composition, electron microscopic appearance, and genomic RNA content. On the basis of these results, we propose a model for the EAV particle in which the GP(2b)/GP(3)/GP(4) heterotrimers are positioned, in association with a defined number of E molecules, above the vertices of the putatively icosahedral nucleocapsid.

Animals↗
PubMed1996

T-banding pattern of bovine chromosomes and karyotype reconstitution with physically mapped cosmids.

Bovine T-banded chromosomes were identified by fluorescence in situ hybridization (FISH) using 27 cosmid probes as chromosome landmarks. Pairwise combinations of probes from chromosomes of markedly different size were cohybridized to metaphase spreads of T-banded chromosomes. This confirmed the association of banding patterns to individual chromosomes. The T-banding pattern appears to be related to R-bands: 80% of T-bands were in corresponding position to R-bands, but not always conserved in size. Band assignments placed 20 probes on similar bands in both patterns. The identification of T-banded chromosomes represents a first step toward the construction of a compositional map of the bovine genome and an additional tool for its study on a comparative basis.

Animals↗
PubMedDate not supplied

Soybean virus Z: its characteristics and taxonomy.

Soybean virus Z is a hitherto undescribed virus of soybeans found in Australia. It has a limited host range, attains a low concentration in plants and has a thermal inactivation point of 65 degrees. It has flexuous filamentous particles with a modal length of 610 nm and forms amorphous inclusions, but no pinwheels, in infected cells. It has not been transmitted by aphids or by seed. Its genome is RNA with the composition G23, A26, C25, U26, and its coat protein weights about 2.7 X 104. This virus seems to be unrelated to previously described viruses of soybeans, and does not fall into any of the described virus groups with similar particles.

Plant Viruses↗
PubMed2006

Protein synthesis inhibitors, in synergy with 5-azacytidine, restore sodium/iodide symporter gene expression in human thyroid adenoma cell line, KAK-1, suggesting trans-active transcriptional repressor.

CONTEXT: Therapy of thyroid carcinoma uses its radioiodine concentration ability for treatment. Dedifferentiated cells lose radioiodine uptake from human sodium-iodide symporter (hNIS) gene transcription failure consequent to genomic structure (chromatin compaction) and composition (CpG methylation). OBJECTIVE AND METHODS: We explored restoring hNIS expression in human thyroid carcinoma cells using thyroid adenoma and carcinoma cell lines: KAK-1, NPA87, BHT-101, and KAT-4B, with quantitative RT-PCR, chromatin immunoprecipitation, deoxyribonuclease I sensitivity assays, and luciferase reporter construct transfections containing hNIS promoter regions. RESULTS: Combined 5-azacytidine and sodium butyrate restores hNIS gene transcription in KAK-1 to levels approaching radioiodine-treatable tumors. Despite induction of H4 acetylation, there was no deoxyribonuclease I sensitivity enhancement in two regions of the hNIS gene promoter. Cycloheximide in cells transfected with luciferase reporter construct, 1.3 kb hNIS gene promoter, stimulated normalized luciferase expression, singly and synergistically with 5-azacytidine, in a dose-dependent, time course-dependent, cell type-specific, and promoter-specific fashion. Both anisomycin and emetine, but not puromycin, had similar effects. Cycloheximide also increased endogenous hNIS mRNA. Transfections with reporter constructs containing consecutive deletions of hNIS gene promoter sequences revealed responsible sequences at -427 to -131 bp. Deletion of 1.2 kb promoter region upstream of -131 bp enhanced basal luciferase reporter activity 3-fold above the activity of full length promoter construct, supporting inhibitory properties of this region. CONCLUSIONS: This suggests that trans-active protein factor(s) represses endogenous hNIS transcription in KAK-1 cells under basal conditions, accounting for loss of iodine uptake. Inhibition of this repressive activity increases endogenous hNIS transcription and presents a novel target to restore hNIS expression in dedifferentiated thyroid carcinoma.

Adenoma↗
PubMed2006

Complete assignment of structural genes involved in flavonoid biosynthesis influencing bulb color to individual chromosomes of the shallot (Allium cepa L.).

We analyzed Japanese bunching onion (Allium fistulosum L.) - shallot (Allium cepa L. Aggregatum group) alien chromosome addition lines in order to assign the genes involved in the flavonoid biosynthesis pathway to chromosomes of the shallot. Two complete sets of alien monosomic additions (2n = 2x + 1 = 17) were used for determining the chromosomal locations of several partial sequences of candidate genes, CHS, CHI, F3H, DFR, and ANS via analyses of PCR-based markers. The results of DNA marker analyses showed that the CHS-A, CHS-B, CHI, F3H, DFR, and ANS genes should be assigned to chromosomes 2A, 4A, 3A, 3A, 7A, and 4A, respectively. HPLC analyses of 14 A. fistulosum - shallot multiple alien additions (2n = 2x + 2 - 2x + 7 = 18 - 23) were conducted to identify the anthocyanin compounds produced in the scaly leaves. A direct comparison between the genomic constitution and the anthocyanin compositions of the multiple additions revealed that a 3GT gene for glucosylation of anthocyanidin was located on 4A. Thus, we were able to assign all structural genes involved in flavonoid biosynthesis influencing bulb color to individual chromosomes of A. cepa.

Acyltransferases↗
PubMed2005

Ancient origin and gene mosaicism of the progenitor of Mycobacterium tuberculosis.

The highly successful human pathogen Mycobacterium tuberculosis has an extremely low level of genetic variation, which suggests that the entire population resulted from clonal expansion following an evolutionary bottleneck around 35,000 y ago. Here, we show that this population constitutes just the visible tip of a much broader progenitor species, whose extant representatives are human isolates of tubercle bacilli from East Africa. In these isolates, we detected incongruence among gene phylogenies as well as mosaic gene sequences, whose individual elements are retrieved in classical M. tuberculosis. Therefore, despite its apparent homogeneity, the M. tuberculosis genome appears to be a composite assembly resulting from horizontal gene transfer events predating clonal expansion. The amount of synonymous nucleotide variation in housekeeping genes suggests that tubercle bacilli were contemporaneous with early hominids in East Africa, and have thus been coevolving with their human host much longer than previously thought. These results open novel perspectives for unraveling the molecular bases of M. tuberculosis evolutionary success.

Journal Article↗
PubMed1989

Mouse angiotensin-converting enzyme is a protein composed of two homologous domains.

Angiotensin-converting enzyme (ACE) is a dipeptidyl carboxypeptidase that converts angiotensin I into the potent vasoconstrictor angiotensin II. We have used cDNA and genomic sequences to assemble a composite cDNA, ACE.315, encoding the entire amino acid sequence of mouse converting enzyme. ACE.315 contains 4838 base pairs and encodes a protein of 1278 amino acids (147.4 kDa) after removal of a 34-amino acid signal peptide. Within the protein, there are two large areas of homologous sequence, each containing a potential Zn-binding region and catalytic site. These homologous regions are approximately half the size of the whole ACE protein and suggest that the modern ACE gene is the duplicated product of a precursor gene. Mouse ACE is 83% homologous to human ACE in both nucleic acid and amino acid sequence, and like human ACE, contains a hydrophobic region in the carboxyl terminus that probably anchors the enzyme to the cell membrane (Soubrier, F., Alhenc-Gelas, F., Hubert, C., Allegrini, J., John, M., Tregear, G., and Corvol, P. (1988) Proc. Natl. Acad. Sci. U.S.A. 85, 9386-9390). Northern analysis of mouse kidney, lung, and testis RNA demonstrates that the testicular isozyme of ACE is encoded by a single, smaller RNA (2500 bases) than the two message sizes found in kidney or lung (4900 and 4150 bases), and that this testicular RNA hybridizes to the 3' portion of ACE.315.

Amino Acid Sequence↗
PubMed1987

The gene for mouse epidermal filaggrin precursor. Its partial characterization, expression, and sequence of a repeating filaggrin unit.

Filaggrin is an important keratin intermediate filament-associated protein of terminally differentiated mammalian epidermis. Its aberrant expression has been implicated in a number of keratinizing disorders. We have isolated and sequenced a cDNA clone to mouse filaggrin, of 1.479 kilobase pairs, which represents less than 10% of the full-length mRNA estimated by Northern blot analysis to be 17 kilobases long. The cDNA clone delineates a 744-base pair repeat. This encodes a protein of 248 amino acids or 26,330 Da, which is almost identical to the known properties of mouse filaggrin in size, amino acid composition, and charge. Total mouse genomic DNA and the filaggrin gene isolated from a cosmid library were found to contain a super-stoichiometric repeat of the same size. These data support the hypothesis (Haydock, P.V., and Dale, B.A. (1986) J. Biol. Chem. 261, 12520-12525) that filaggrin is initially synthesized as a polyprotein precursor containing many tandem copies. However, our data suggest that the repeating filaggrin units of the precursor are not separated by "large linker" peptides as suggested by these authors. In situ hybridization was used to show that the filaggrin precursor mRNA is located precisely over the granular layer of the epidermis, indicating that expression of this gene is regulated at the transcriptional level as for the differentiation-specific keratin 1 protein. These probes will now permit detailed studies on the regulation of expression of the filaggrin gene.

Amino Acids↗
PubMed1989

Deviations from expected frequencies of CpG dinucleotides in herpesvirus DNAs may be diagnostic of differences in the states of their latent genomes.

The DNA sequences of genomes from G + C-rich and A + T-rich lymphotropic herpesviruses [i.e. gammaherpesviruses; Epstein-Barr virus and herpesvirus saimiri (HVS)] are deficient in CpG dinucleotides and contain an excess of TpG and CpA dinucleotides relative to frequencies predicted from their mononucleotide compositions. In contrast, for sequences from genomes of G + C-rich and A + T-rich neurotropic herpesviruses (i.e. alphaherpesviruses; herpes simplex virus and varicellazoster virus) and human cytomegalovirus (HCMV; a betaherpesvirus) the mean observed frequencies of these dinucleotides are close to those expected from their mononucleotide compositions. Comparisons between DNA sequences that encode proteins conserved in all these viruses also show that sequences of these lymphotropic viruses are CpG-deficient whereas the homologous genes from the neurotropic viruses and the HCMV are not. Analyses of local variations in dinucleotide frequencies reveal some occurrences of clustered CpG dinucleotides in generally deficient genomes (e.g. upstream of the thymidylate synthase gene of HVS) and locally CpG-deficient regions within some generally non-deficient genomes (e.g. the major immediate early genes of human, simian and murine CMVs). A relative deficiency in CpG and an excess of TpG and CpA dinucleotides is a diagnostic feature of higher eukaryotic DNA sequences that have been subjected to methylation of cytosine residues in CpG doublets with the resulting increase in mutations to give TpG (and thereby its complement, CpA). The available evidence implicates the latent genome as the site of methylation of these herpesviruses. We conclude that in the neurotropic herpesviruses the normal latent precursors to infectious progeny are not methylated whereas there is local methylation of the immediate early locus in the latent genomes of CMVs, and the latent genomes of these lymphotropic herpesviruses are extensively methylated.

Base Sequence↗