Showing papers on "Chromosome published in 2006"
TL;DR: It is demonstrated here that active and inactive genes are engaged in many long-range intrachromosomal interactions and can also form interchromosomal contacts and establish 4C technology as a powerful tool to study nuclear architecture.
Abstract: The spatial organization of DNA in the cell nucleus is an emerging key contributor to genomic function1,2,3,4,5,6,7,8,9,10,11,12. We developed 4C technology (chromosome conformation capture (3C)-on-chip), which allows for an unbiased genome-wide search for DNA loci that contact a given locus in the nuclear space. We demonstrate here that active and inactive genes are engaged in many long-range intrachromosomal interactions and can also form interchromosomal contacts. The active β-globin locus in fetal liver preferentially contacts transcribed, but not necessarily tissue-specific, loci elsewhere on chromosome 7, whereas the inactive locus in fetal brain contacts different transcriptionally silent loci. A housekeeping gene in a gene-dense region on chromosome 8 forms long-range contacts predominantly with other active gene clusters, both in cis and in trans, and many of these intra- and interchromosomal interactions are conserved between the tissues analyzed. Our data demonstrate that chromosomes fold into areas of active chromatin and areas of inactive chromatin and establish 4C technology as a powerful tool to study nuclear architecture.
1,354 citations
TL;DR: It is suggested that local chromatin conformation and gene transcription influence the extent with which chromosomes interact and affect their overall properties, with direct consequences for cell-type specific genome stability.
Abstract: After mitosis, mammalian chromosomes partially decondense to occupy distinct territories in the cell nucleus. Current models propose that territories are separated by an interchromatin domain, rich in soluble nuclear machinery, where only rare interchromosomal interactions can occur via extended chromatin loops. In contrast, recent evidence for chromatin mobility and high frequency of chromosome translocations are consistent with significant levels of chromosome intermingling, with important consequences for genome function and stability. Here we use a novel high-resolution in situ hybridization procedure that preserves chromatin nanostructure to show that chromosome territories intermingle significantly in the nucleus of human cells. The degree of intermingling between specific chromosome pairs in human lymphocytes correlates with the frequency of chromosome translocations in the same cell type, implying that double-strand breaks formed within areas of intermingling are more likely to participate in interchromosomal rearrangements. The presence of transcription factories in regions of intermingling and the effect of transcription impairment on the interactions between chromosomes shows that transcription-dependent interchromosomal associations shape chromosome organization in mammalian cells. These findings suggest that local chromatin conformation and gene transcription influence the extent with which chromosomes interact and affect their overall properties, with direct consequences for cell-type specific genome stability.
711 citations
TL;DR: It is shown that CENP-A nucleosomes directly recruit a proximal CEN parenthood-associated nucleosome associated complex (NAC) comprised of three new human centromere proteins (CENp-M, CenP-N and CENT-T), along with C ENP-U(50), CEN P-C and C ENp-H.
Abstract: The basic element for chromosome inheritance, the centromere, is epigenetically determined in mammals. The prime candidate for specifying centromere identity is the array of nucleosomes assembled with CENP-A, the centromere-specific histone H3 variant. Here, we show that CENP-A nucleosomes directly recruit a proximal CENP-A nucleosome associated complex (NAC) comprised of three new human centromere proteins (CENP-M, CENP-N and CENP-T), along with CENP-U(50), CENP-C and CENP-H. Assembly of the CENP-A NAC at centromeres is dependent on CENP-M, CENP-N and CENP-T. Facilitates chromatin transcription (FACT) and nucleophosmin-1 (previously implicated in transcriptional chromatin remodelling and as a multifunctional nuclear chaperone, respectively) are absent from histone H3-containing nucleosomes, but are stably recruited to CENP-A nucleosomes independent of CENP-A NAC. Seven new CENP-A-nucleosome distal (CAD) centromere components (CENP-K, CENP-L, CENP-O, CENP-P, CENP-Q, CENP-R and CENP-S) are identified as assembling on the CENP-A NAC. The CENP-A NAC is essential, as disruption of the complex causes errors of chromosome alignment and segregation that preclude cell survival despite continued centromere-derived mitotic checkpoint signalling.
676 citations
TL;DR: Increase and decreases in drug resistance were strongly associated with gain and loss of this isochromosome, which bears genes expressing the enzyme in the ergosterol pathway targeted by azole drugs, efflux pumps, and a transcription factor that positively regulates a subset of efflux pump genes.
Abstract: Resistance to the limited number of available antifungal drugs is a serious problem in the treatment of Candida albicans. We found that aneuploidy in general and a specific segmental aneuploidy, consisting of an isochromosome composed of the two left arms of chromosome 5, were associated with azole resistance. The isochromosome forms around a single centromere flanked by an inverted repeat and was found as an independent chromosome or fused at the telomere to a full-length homolog of chromosome 5. Increases and decreases in drug resistance were strongly associated with gain and loss of this isochromosome, which bears genes expressing the enzyme in the ergosterol pathway targeted by azole drugs, efflux pumps, and a transcription factor that positively regulates a subset of efflux pump genes.
652 citations
TL;DR: This work has shown that chromosomes in the cell nucleus are organized as chromosome territories, and present models of chromosome territory architecture differ widely with respect to the possible functional implications of dynamic changes of this architecture during the cell cycle and terminal cell differentiation.
590 citations
TL;DR: The analysis shows that α-gliadin sequences from the three genomes of bread wheat form distinct groups, indicating that the three genome contribute differently to epitope content.
Abstract: Bread wheat (Triticum aestivum) is an important staple food. However, wheat gluten proteins cause celiac disease (CD) in 0.5 to 1% of the general population. Among these proteins, the α-gliadins contain several peptides that are associated to the disease. We obtained 230 distinct α-gliadin gene sequences from severaldiploid wheat species representing the ancestral A, B, and D genomes of the hexaploid bread wheat. The large majority of these sequences (87%) contained an internal stop codon. All α-gliadin sequences could be distinguished according to the genome of origin on the basis of sequence similarity, of the average length of the polyglutamine repeats, and of the differences in the presence of four peptides that have been identified as T cell stimulatory epitopes in CD patients through binding to HLA-DQ2/8. By sequence similarity, α-gliadins from the public database of hexaploid T. aestivum could be assigned directly to chromosome 6A, 6B, or 6D. T. monococcum (A genome) sequences, as well as those from chromosome 6A of bread wheat, almost invariably contained epitope glia-α9 and glia-α20, but never the intact epitopes glia-α and glia-α2. A number of sequences from T. speltoides, as well as a number of sequences fromchromosome 6B of bread wheat, did not contain any of the four T cell epitopes screened for. The sequences from T. tauschii (D genome), as well as those from chromosome 6D of bread wheat, were found to contain all of these T cell epitopes in variable combinations per gene. The differences in epitope composition resulted mainly from point mutations. These substitutions appeared to be genome specific. Our analysis shows that α-gliadin sequences from the three genomes of bread wheat form distinct groups. The four known T cell stimulatory epitopes are distributed non-randomly across the sequences, indicating that the three genomes contribute differently to epitope content. A systematic analysis of all known epitopes in gliadins and glutenins will lead to better understanding of the differences in toxicity among wheat varieties. On the basis of such insight, breeding strategies can be designed to generate less toxic varieties of wheat which may be tolerated by at least part of the CD patient population.
568 citations
TL;DR: This work localized Ph1 to a 2.5-megabase interstitial region of wheat chromosome 5B containing a structure consisting of a segment of subtelomeric heterochromatin that inserted into a cluster of cdc2-related genes after polyploidization.
Abstract: The foundation of western civilization owes much to the high fertility of bread wheat, which results from the stability of its polyploid genome. Despite possessing multiple sets of related chromosomes, hexaploid (bread) and tetraploid (pasta) wheat both behave as diploids at meiosis. Correct pairing of homologous chromosomes is controlled by the Ph1 locus. In wheat hybrids, Ph1 prevents pairing between related chromosomes. Lack of Ph1 activity in diploid relatives of wheat suggests that Ph1 arose on polyploidization. Absence of phenotypic variation, apart from dosage effects, and the failure of ethylmethane sulphonate treatment to yield mutants, indicates that Ph1 has a complex structure. Here we have localized Ph1 to a 2.5-megabase interstitial region of wheat chromosome 5B containing a structure consisting of a segment of subtelomeric heterochromatin that inserted into a cluster of cdc2-related genes after polyploidization. The correlation of the presence of this structure with Ph1 activity in related species, and the involvement of heterochromatin with Ph1 (ref. 6) and cdc2 genes with meiosis, makes the structure a good candidate for the Ph1 locus.
475 citations
TL;DR: A contiguous 40 kb fragment of the S. typhimurium chromosome which encodes invasion genes is absent from the corresponding region of the E. coli K‐12 chromosome and may represent a pathogenicity island and it is speculated that acquisition of the 40 kb region must have significantly advanced the evolution of Salmonella as a pathogenic.
Abstract: Summary
Many Salmonella typhimurium genes are required for bacterial entry into host cells. P22 transduction analysis has localized several invasion loci near minute 59 on the S. typhimurium chromosome. To further characterize the 59–60 min chromosomal region, we determined the physical and genetic map of 85 kb of S. typhimurium DNA between srl and cysC. It was previously shown that some of the invasion genes from this region are not present in Escherichia coli K-12. We examined whether other S. typhimurium genes on the 85 kb of DNA were similarly absent from E. coli We found that a contiguous 40 kb fragment of the S. typhimurium chromosome which encodes invasion genes is absent from the corresponding region of the E. coli K-12 chromosome and may represent a pathogenicity island. We speculate that acquisition of the 40 kb region must have significantly advanced the evolution of Salmonella as a pathogen.
391 citations
TL;DR: A number of findings support the hypothesis of a predictive association between the frequency of MN in cytokinesis-blocked lymphocytes and cancer development.
343 citations
TL;DR: It is expected that FISH will continue to play an important role in relating DNA sequence information to chromosome biology and FISH coupled with immunoassays will be increasingly used to study features of chromatin at the cytological level that control expression and regulation of genes.
Abstract: Fluorescence in situ hybridization (FISH), which allows direct mapping of DNA sequences on chromosomes, has become the most important technique in plant molecular cytogenetics research. Repetitive DNA sequence can generate unique FISH patterns on individual chromosomes for karyotyping and phylogenetic analysis. FISH on meiotic pachytene chromosomes coupled with digital imaging systems has become an efficient method to develop physical maps in plant species. FISH on extended DNA fibers provides a high-resolution mapping approach to analyze large DNA molecules and to characterize large genomic loci. FISH-based physical mapping provides a valuable complementary approach in genome sequencing and map-based cloning research. We expect that FISH will continue to play an important role in relating DNA sequence information to chromosome biology. FISH coupled with immunoassays will be increasingly used to study features of chromatin at the cytological level that control expression and regulation of genes.
299 citations
TL;DR: By using dicentrics from dispensable chromosomes, centromere inactivation was found to be quite common under these circumstances.
Abstract: Somatic chromosome spreads from maize (Zea mays L.) plants containing B-A translocation chromosomes undergoing the chromosome type breakage-fusion-bridge cycle were examined by FISH. The size and type of extra chromosomes varied among cells of the same individual. A collection of minichromosomes derived from the chromosome type breakage-fusion-bridge cycle was examined for the presence of stable dicentric chromosomes. Six of 23 chromosomes in the collection contained two regions with DNA sequences typical of centromeres. Functional analysis and immunolabeling of CENH3, the centromere-specific histone H3 variant, revealed only one functional centromere per chromosome, despite the duplicate centromere sequences. One plant was found with an inactive B centromere that had been translocated to the short arm of chromosome 9. The translocated centromere region appeared identical to that of a normal B chromosome. The inactivation of the centromeres was stable for at least four generations. By using dicentrics from dispensable chromosomes, centromere inactivation was found to be quite common under these circumstances.
TL;DR: The differentiation of sex chromosomes was probably initiated from the distal region on the short arm of the protosex chromosome of the common ancestor, and then deletion and heterochromatization progressed on the sex-specific chromosome from the phylogenetically primitive boids to the more advanced viperids.
Abstract: All snake species exhibit genetic sex determination with the ZZ/ZW type of sex chromosomes. To investigate the origin and evolution of snake sex chromosomes, we constructed, by FISH, a cytogenetic map of the Japanese four-striped rat snake (Elaphe quadrivirgata) with 109 cDNA clones. Eleven of the 109 clones were localized to the Z chromosome. All human and chicken homologues of the snake Z-linked genes were located on autosomes, suggesting that the sex chromosomes of snakes, mammals, and birds were all derived from different autosomal pairs of the common ancestor. We mapped the 11 Z-linked genes of E. quadrivirgata to chromosomes of two other species, the Burmese python (Python molurus bivittatus) and the habu (Trimeresurus flavoviridis), to investigate the process of W chromosome differentiation. All and 3 of the 11 clones were localized to both the Z and W chromosomes in P. molurus and E. quadrivirgata, respectively, whereas no cDNA clones were mapped to the W chromosome in T. flavoviridis. Comparative mapping revealed that the sex chromosomes are only slightly differentiated in P. molurus, whereas they are fully differentiated in T. flavoviridis, and E. quadrivirgata is at a transitional stage of sex-chromosome differentiation. The differentiation of sex chromosomes was probably initiated from the distal region on the short arm of the protosex chromosome of the common ancestor, and then deletion and heterochromatization progressed on the sex-specific chromosome from the phylogenetically primitive boids to the more advanced viperids.
TL;DR: In this paper, the authors reported 5 cases (World Health Organization grade III) in which metaphase cytogenetics identified a derivative chromosome consisting of what appears to be the whole arms of 1q and 19p forming a der(1;19)(q10;p10).
Abstract: Deletions of portions of chromosomes 1p and 19q are closely associated with the oligodendroglioma histologic phenotype. In most cases, 1p and 19q are codeleted, yet the mechanism of dual loss is unexplained. We report 5 cases (World Health Organization grade III) in which metaphase cytogenetics identified a derivative chromosome consisting of what appears to be the whole arms of 1q and 19p forming a der(1;19)(q10;p10). Metaphase fluorescent in situ hybridization (FISH) confirmed the derivative chromosome was composed of 1q and 19p material in 3 cases; in 2 cases with few metaphases, FISH confirmed 19p material on the derivative chromosome. In all cases, interphase FISH showed net loss of 1p and 19q in 77% to 92% of cells, and microsatellite studies were consistent with 1p and 19q loss. We hypothesize the following: occurrence of a balanced whole-arm translocation between chromosomes 1 and 19 forming 2 derivative chromosomes, one composed of 1q and 19p, the other of 1p and 19q. Subsequent loss of the der(1;19)(p10;q10) then results in the simultaneous 1p and 19q loss observed in oligodendroglioma with retention of the der(1;19)(q10;p10) seen in these cases.
TL;DR: Visualization of pairwise combinations of multiple genetic loci reveals that the two replichores occupy separate nucleoid halves, with the replication origin between; positions of loci on each replichore recapitulate the genetic map.
Abstract: DNA replication divides the circular Escherichia coli chromosome into equal arms (replichores). Visualization of pairwise combinations of multiple genetic loci reveals that the two replichores occupy separate nucleoid halves, with the replication origin between; positions of loci on each replichore recapitulate the genetic map. Sequential replication-segregation regenerates the structure by sequentially layering newly replicated replichore DNA to specific inner and outer edges of the developing sister nucleoids. Replication fork-dependent locus positions are imprinted, so that in most generations the chromosome orientation in a mother cell is recreated as a arrangement of sister chromosomes in daughter cells.
TL;DR: The mechanisms of methylation induced premeiotically, repeat-induced point mutation, meiotic silencing by unpaired DNA, and meiotic sex chromosome inactivation will be discussed and the multiple mechanisms suggested to contribute to homologous pairing are analyzed.
Abstract: This review focuses on various aspects of chromosome homology searching and their relationship to meiotic and vegetative pairing and to the silencing of unpaired copies of genes. Chromosome recognition and pairing is a prominent characteristic of meiosis; however, for some organisms, this association (complete or partial) is also a normal part of nuclear organization. The multiple mechanisms suggested to contribute to homologous pairing are analyzed. Recognition of DNA/DNA homology also plays an important role in detecting DNA segments that are present in inappropriate number of copies before and during meiosis. In this context, the mechanisms of methylation induced premeiotically, repeat-induced point mutation, meiotic silencing by unpaired DNA, and meiotic sex chromosome inactivation will be discussed. Homologue juxtaposition during meiotic prophase can be divided into three mechanistically distinct steps, namely, recognition, presynaptic alignment, and synapsis by the synaptonemal complex (SC). In most organisms, these three steps are distinguished by their dependence on DNA double-strand breaks (DSBs). The coupling of SC initiation to (and downstream effects of) DSB formation and the exceptions to this dependency are discussed. Finally, this review addresses the specific factors that appear to promote chromosome movement at various stages of meiotic prophase, most particularly at the bouquet stage, and on their significance for homologue pairing and/or achieving a final pachytene configuration.
TL;DR: Evidence is presented that the Smc5/6 complex is needed during replication to prevent the accumulation of branched chromosome structures and that the complex's role in unchallenged cells is independent of DNA damage.
TL;DR: Principal component analysis showed that CO rates negatively correlate with the G+C content, in contrast to that reported in other eukaryotes, and "hot spots" of meiotic recombination contained in small fragments of a few kilobases are revealed.
Abstract: Crossover (CO) is a key process for the accurate segregation of homologous chromosomes during the first meiotic division. In most eukaryotes, meiotic recombination is not homogeneous along the chromosomes, suggesting a tight control of the location of recombination events. We genotyped 71 single nucleotide polymorphisms (SNPs) covering the entire chromosome 4 of Arabidopsis thaliana on 702 F2 plants, representing 1404 meioses and allowing the detection of 1171 COs, to study CO localization in a higher plant. The genetic recombination rates varied along the chromosome from 0 cM/Mb near the centromere to 20 cM/Mb on the short arm next to the NOR region, with a chromosome average of 4.6 cM/Mb. Principal component analysis showed that CO rates negatively correlate with the G+C content (P = 3x10(-4)), in contrast to that reported in other eukaryotes. COs also significantly correlate with the density of single repeats and the CpG ratio, but not with genes, pseudogenes, transposable elements, or dispersed repeats. Chromosome 4 has, on average, 1.6 COs per meiosis, and these COs are subjected to interference. A detailed analysis of several regions having high CO rates revealed "hot spots" of meiotic recombination contained in small fragments of a few kilobases. Both the intensity and the density of these hot spots explain the variation of CO rates along the chromosome.
TL;DR: The strategy to find fertility factors conserved from C. elegans to mammals achieved its goal: of mouse gene knockouts corresponding to nematode proteins, 37% (7/19) cause male sterility and provides significant opportunity to identify causes of male infertility and targets for male contraceptives.
Abstract: Male infertility is a long-standing enigma of significant medical concern. The integrity of sperm chromatin is a clinical indicator of male fertility and in vitro fertilization potential: chromosome aneuploidy and DNA decondensation or damage are correlated with reproductive failure. Identifying conserved proteins important for sperm chromatin structure and packaging can reveal universal causes of infertility. Here we combine proteomics, cytology and functional analysis in Caenorhabditis elegans to identify spermatogenic chromatin-associated proteins that are important for fertility. Our strategy employed multiple steps: purification of chromatin from comparable meiotic cell types, namely those undergoing spermatogenesis or oogenesis; proteomic analysis by multidimensional protein identification technology (MudPIT) of factors that co-purify with chromatin; prioritization of sperm proteins based on abundance; and subtraction of common proteins to eliminate general chromatin and meiotic factors. Our approach reduced 1,099 proteins co-purified with spermatogenic chromatin, currently the most extensive catalogue, to 132 proteins for functional analysis. Reduction of gene function through RNA interference coupled with protein localization studies revealed conserved spermatogenesis-specific proteins vital for DNA compaction, chromosome segregation, and fertility. Unexpected roles in spermatogenesis were also detected for factors involved in other processes. Our strategy to find fertility factors conserved from C. elegans to mammals achieved its goal: of mouse gene knockouts corresponding to nematode proteins, 37% (7/19) cause male sterility. Our list therefore provides significant opportunity to identify causes of male infertility and targets for male contraceptives.
TL;DR: The 8-9-Mb Streptomyces chromosome is linear, with a "core" containing essential genes and "arms" carrying conditionally adaptive genes that can sustain large deletions in the laboratory.
Abstract: The 8-9-Mb Streptomyces chromosome is linear, with a "core" containing essential genes and "arms" carrying conditionally adaptive genes that can sustain large deletions in the laboratory. Bidirectional chromosome replication from a central oriC is completed by "end-patching," primed from terminal proteins covalently bound to the free 5'-ends. Plasmid-mediated conjugation involves movement of double-stranded DNA by proteins resembling other bacterial motor proteins, probably via hyphal tip fusion, mediated by these transfer proteins. Circular plasmids probably transfer chromosomes by transient integration, but linear plasmids may lead the donor chromosome end-first into the recipient by noncovalent association of ends. Transfer of complete chromosomes may be the rule. The recipient mycelium is colonized by intramycelial spreading of plasmid copies, under the control of plasmid-borne "spread" genes. Chromosome partition into prespore compartments of the aerial mycelium is controlled in part by actin- and tubulin-like proteins, resembling MreB and FtsZ of other bacteria.
TL;DR: Studies on the organization of homogeneous arrays of chromosome-specific alpha-satellite repeats and evolutionary links among eukaryotic centromeric sequences are reviewed.
Abstract: Centromeres are the elements of chromosomes that assemble the proteinaceous kinetochore, maintain sister chromatid cohesion, regulate chromosome attachment to the spindle, and direct chromosome movement during cell division. Although the functions of centromeres and the proteins that contribute to their complex structure and function are conserved in eukaryotes, centromeric DNA diverges rapidly. Human centromeres are particularly complicated. Here, we review studies on the organization of homogeneous arrays of chromosome-specific alpha-satellite repeats and evolutionary links among eukaryotic centromeric sequences. We also discuss epigenetic mechanisms of centromere identity that confer structural and functional features of the centromere through DNA-protein interactions and post-translational modifications, producing centromere-specific chromatin signatures. The assembly and organization of human centromeres, the contributions of satellite DNA to centromere identity and diversity, and the mechanism whereby centromeres are distinguished from the rest of the genome reflect ongoing puzzles in chromosome biology.
TL;DR: The results indicate that polyploidy might be more widespread in archaea (or even prokaryotes in general) than previously assumed, and the presence of so many genome copies in a proKaryote raises questions about the evolutionary significance of this strategy.
Abstract: Polyploidy is common in higher eukaryotes, especially in plants, but it is generally assumed that most prokaryotes contain a single copy of a circular chromosome and are therefore monoploid. We have used two independent methods to determine the genome copy number in halophilic archaea, 1) cell lysis in agarose blocks and Southern blot analysis, and 2) Real-Time quantitative PCR. Fast growing H. salinarum cells contain on average about 25 copies of the chromosome in exponential phase, and their ploidy is downregulated to 15 copies in early stationary phase. The chromosome copy number is identical in cultures with a twofold lower growth rate, in contrast to the results reported for several other prokaryotic species. Of three additional replicons of H. salinarum, two have a low copy number that is not growth-phase regulated, while one replicon even shows a higher degree of growth phase-dependent regulation than the main replicon. The genome copy number of H. volcanii is similarly high during exponential phase (on average 18 copies/cell), and it is also downregulated (to 10 copies) as the cells enter stationary phase. The variation of genome copy numbers in the population was addressed by fluorescence microscopy and by FACS analysis. These methods allowed us to verify the growth phase-dependent regulation of ploidy in H. salinarum, and they revealed that there is a wide variation in genome copy numbers in individual cells that is much larger in exponential than in stationary phase. Our results indicate that polyploidy might be more widespread in archaea (or even prokaryotes in general) than previously assumed. Moreover, the presence of so many genome copies in a prokaryote raises questions about the evolutionary significance of this strategy.
TL;DR: The loss of a single telomere can generate a wide variety of chromosome alterations commonly associated with human cancer, not only on the chromosome that originally lost its telomeres, but other chromosomes as well.
TL;DR: Using purified components, it is found that Spo0J has the ability to coat non‐specific DNA substrates and these ‘Spo0J domains’ provide large structures near oriC that could potentially demark, organize or localize the origin region of the chromosome.
Abstract: Summary Regulation of chromosome inheritance is essential to ensure proper transmission of genetic information. To accomplish accurate genome segregation, cells organize their chromosomes and actively separate them prior to cytokinesis. In Bacillus subtilis the Spo0J protein is required for accurate chromosome segregation and it regulates the developmental switch from vegetative growth to sporulation. Spo0J is a DNA-binding protein that recognizes at least eight identified parS sites located near the origin of replication. As judged by fluorescence microscopy, Spo0J forms discrete foci associated with the oriC region of the chromosome throughout the cell cycle. In an attempt to determine the mechanisms utilized by Spo0J to facilitate productive chromosome segrega- tion, we have investigated the DNA binding activity of Spo0J. In vivo we find Spo0J associates with several kilobases of DNA flanking its specific binding sites (parS) through a parS-dependent nucleation event that promotes lateral spreading of Spo0J along the chromosome. Using purified components we find that Spo0J has the ability to coat non-specific DNA substrates. These 'Spo0J domains' provide large structures near oriC that could potentially demark, organize or localize the origin region of the chromosome.
TL;DR: Interestingly the non-recombining part of the Y did not spread out considerably from the original duplicated fragment, possibly because of a large sequence duplication bordering the Y-specific fragment, and provides insights into some of the initial processes of Y chromosome evolution.
Abstract: Sequencing of the human Y chromosome has uncovered the peculiarities of the genomic organization of a heterogametic sex chromosome of old evolutionary age, and has led to many insights into the evolutionary changes that occurred during its long history. We have studied the genomic organization of the medaka fish Y chromosome, which is one of the youngest heterogametic sex chromosomes on which molecular data are available. The Y specific and adjacent regions were sequenced and compared to the X. The male sex-determining gene, dmrt1bY, appears to be the only functional gene in the Y-specific region. The Y-specific region itself is derived from the duplication of a 43-kb fragment from linkage group 9. All other coduplicated genes except dmrt1bY degenerated. The Y-specific region has accumulated large stretches of repetitive sequences and duplicated pieces of DNA from elsewhere in the genome, thereby growing to 258 kb. Interestingly the non-recombining part of the Y did not spread out considerably from the original duplicated fragment, possibly because of a large sequence duplication bordering the Y-specific fragment. This may have conserved the more ancestral structure of the medaka Y and provides insights into some of the initial processes of Y chromosome evolution.
TL;DR: It is suggested that distinct but characteristic forms of nuclear genome organization are required for genome reprogramming in early embryos and for proper regulation of differential gene expression patterns at later stages.
TL;DR: This review will be focused on the chromosomal aberrations involving the TTAGGG sequence, i.e., the telomeric repeat sequence that "caps" the chromosomes of all vertebrate species.
Abstract: Telomeres are specialized nucleoproteic complexes localized at the physical ends of linear eukaryotic chromosomes that maintain their stability and integrity. The DNA component of telomeres is characterized by being a G-rich double stranded DNA composed by short fragments tandemly repeated with different sequences depending on the species considered. At the chromosome level, telomeres or, more properly, telomeric repeats--the DNA component of telomeres--can be detected either by using the fluorescence in situ hybridization (FISH) technique with a DNA or a peptide nucleic acid (PNA) (pan)telomeric probe, i.e., which identifies simultaneously all of the telomeres in a metaphase cell, or by the primed in situ labeling (PRINS) reaction using an oligonucleotide primer complementary to the telomeric DNA repeated sequence. Using these techniques, incomplete chromosome elements, acentric fragments, amplification and translocation of telomeric repeat sequences, telomeric associations and telomeric fusions can be identified. In addition, chromosome orientation (CO)-FISH allows to discriminate between the different types of telomeric fusions, namely telomere-telomere and telomere-DNA double strand break fusions and to detect recombination events at the telomere, i.e., telomeric sister-chromatid exchanges (T-SCE). In this review, we summarize our current knowledge of chromosomal aberrations involving telomeres and interstitial telomeric repeat sequences and their induction by physical and chemical mutagens. Since all of the studies on the induction of these types of aberrations were conducted in mammalian cells, the review will be focused on the chromosomal aberrations involving the TTAGGG sequence, i.e., the telomeric repeat sequence that "caps" the chromosomes of all vertebrate species.
TL;DR: In this paper, the pairing and recombination pattern of A and C chromosomes during meiosis of Brassica napus triploid hybrids was investigated. But the authors focused on the interspecific cross between natural B. napus and B. rapa.
Abstract: Interspecific crosses contribute significantly to plant evolution enabling gene exchanges between species. The efficiency of interspecific crosses depends on the similarity between the implicated genomes as high levels of genome similarity are required to ensure appropriate chromosome pairing and genetic recombination. Brassica napus (AACC) is an allopolyploid, resulting from natural hybridization between Brassica rapa (AA) and Brassica oleracea (CC), both being diploid species derived from a common ancestor. To study the relationships between genomes of these Brassica species, we have determined simultaneously the pairing and recombination pattern of A and C chromosomes during meiosis of AAC triploid hybrids, which result from the interspecific cross between natural B. napus and B. rapa. Different AAC triploid hybrids and their progenies have been analysed using cytogenetic, BAC-FISH, and molecular techniques. In 71% of the pollen mother cells, homologous A chromosomes paired regularly, and usually one chromosome of each pair was transmitted to the progeny. C chromosomes remained mainly univalent, but were involved in homoeologous pairing in 21.5% of the cells, and 13% of the transmitted C chromosomes were either recombined or broken. The rate of transmission of C chromosomes depended on the identity of the particular chromosome and on the way the hybrid was crossed, as the male or as the female parent, to B. napus or to B. rapa. Gene transfers in triploid hybrids are favoured between A genomes of B. rapa and B. napus, but also occur between A and C genomes though at lower rates.
TL;DR: Abnormalities caused by whole chromosome non-disjunction, unbalanced chromatid predivision and chromosome breakage were reliably identified using the CGH protocol and provided further evidence for the existence of age-independent factors in female aneuploidy.
Abstract: BACKGROUND: Classical cytogenetic methods and fluorescent in situ hybridization (FISH) have been employed for the analysis of chromosomal abnormalities in human oocytes. However, these methods are limited by the need to spread the sample on a microscope slide, a process that risks artefactual chromosome loss. Comparative genomic hybridization (CGH) is a DNA-based method that enables the investigation of the entire chromosome complement. We optimized and evaluated a CGH protocol for the chromosomal analysis of first polar bodies (PBs) and oocytes. The protocol was then employed to obtain a detailed picture of meiosis I errors in human oogenesis. METHODS: 107 MII oocyte-PB complexes were examined using whole genome amplification (WGA) and CGH. RESULTS: Data was obtained for 100 complexes, donated from 46 patients of average age 32.5 (range 18-42). 22 complexes from 15 patients were abnormal, giving an aneuploidy rate of 22 %. CONCLUSIONS: The results presented in this study more than double the quantity of CGH data from female gametes currently available. Abnormalities caused by whole chromosome non-disjunction, unbalanced chromatid predivision and chromosome breakage were reliably identified using the CGH protocol. Analysis of the data revealed a preferential participation of chromosome X and the smaller autosomes in aneuploidy and provided further evidence for the existence of age-independent factors in female aneuploidy.
TL;DR: The data demonstrate the unique information generated by high resolution analysis ofNSCLC genomes and uncover the presence of genetic alterations prevalent in the different NSCLC subtypes.
Abstract: Chromosomal regions harboring tumor suppressors and oncogenes are often deleted or amplified. Array comparative genomic hybridization detects segmental DNA copy number alterations in tumor DNA relative to a normal control. The recent development of a bacterial artificial chromosome array, which spans the human genome in a tiling path manner with >32,000 clones, has facilitated whole genome profiling at an unprecedented resolution. Using this technology, we comprehensively describe and compare the genomes of 28 commonly used non-small cell lung carcinoma (NSCLC) cell models, derived from 18 adenocarcinomas (AC), 9 squamous cell carcinomas and 1 large cell carcinoma. Analysis at such resolution not only provided a detailed genomic alteration template for each of these model cell lines, but revealed novel regions of frequent duplication and deletion. Significantly, a detailed analysis of chromosome 7 identified 6 distinct regions of alterations across this chromosome, implicating the presence of multiple novel oncogene loci on this chromosome. As well, a comparison between the squamous and AC cells revealed alterations common to both subtypes, such as the loss of 3p and gain of 5p, in addition to multiple hotspots more frequently associated with only 1 subtype. Interestingly, chromosome 3q, which is known to be amplified in both subtypes, showed 2 distinct regions of alteration, 1 frequently altered in squamous and 1 more frequently altered in AC. In summary, our data demonstrate the unique information generated by high resolution analysis of NSCLC genomes and uncover the presence of genetic alterations prevalent in the different NSCLC subtypes. © 2005 Wiley-Liss, Inc.
TL;DR: In this article, the authors sequenced the two copies of one such region, generating 7.8 Mb of sequence spanning 17.4 cM of the short arm of chromosome 1 and 6.6 Mb (25.6 cM) from the long arm of chromosomes 9.
Abstract: Maize (Zea mays or corn), both a major food source and an important cytogenetic model, evolved from a tetraploid that arose about 4.8 million years ago (Mya). As a result, maize has extensive duplicated regions within its genome. We have sequenced the two copies of one such region, generating 7.8 Mb of sequence spanning 17.4 cM of the short arm of chromosome 1 and 6.6 Mb (25.6 cM) from the long arm of chromosome 9. Rice, which did not undergo a similar whole genome duplication event, has only one orthologous region (4.9 Mb) on the short arm of chromosome 3, and can be used as reference for the maize homoeologous regions. Alignment of the three regions allowed identification of syntenic blocks, and indicated that the maize regions have undergone differential contraction in genic and intergenic regions and expansion by the insertion of retrotransposable elements. Approximately 9% of the predicted genes in each duplicated region are completely missing in the rice genome, and almost 20% have moved to other genomic locations. Predicted genes within these regions tend to be larger in maize than in rice, primarily because of the presence of predicted genes in maize with larger introns. Interestingly, the general gene methylation patterns in the maize homoeologous regions do not appear to have changed with contraction or expansion of their chromosomes. In addition, no differences in methylation of single genes and tandemly repeated gene copies have been detected. These results, therefore, provide new insights into the diploidization of polyploid species.