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At least 19 recordsLinked to original sources
PubMed2004

The nucleosome: from genomic organization to genomic regulation.

Electron micrographs first confirmed that the eukaryotic genome is organized into repeating disk-shaped nucleosomal units composed of histones and their associated DNA. Those images made clear the function of the nucleosome in packaging and condensing the genome. Today, nucleosomes are recognized as highly dynamic units through which the eukaryotic genome can be regulated with epigenetically heritable consequences. This review focuses on the conserved protein structures that mobilize and remodel nucleosomes and specifically mark and recognize their histone and DNA components. These events directly impact DNA transcription, replication, recombination, and repair.

Amino Acid Sequence↗
PubMed2003

Towards the delineation of the ancestral eutherian genome organization: comparative genome maps of human and the African elephant (Loxodonta africana) generated by chromosome painting.

This study presents a whole-genome comparison of human and a representative of the Afrotherian clade, the African elephant, generated by reciprocal Zoo-FISH. An analysis of Afrotheria genomes is of special interest, because recent DNA sequence comparisons identify them as the oldest placental mammalian clade. Complete sets of whole-chromosome specific painting probes for the African elephant and human were constructed by degenerate oligonucleotide-primed PCR amplification of flow-sorted chromosomes. Comparative genome maps are presented based on their hybridization patterns. These maps show that the elephant has a moderately rearranged chromosome complement when compared to humans. The human paint probes identified 53 evolutionary conserved segments on the 27 autosomal elephant chromosomes and the X chromosome. Reciprocal experiments with elephant probes delineated 68 conserved segments in the human genome. The comparison with a recent aardvark and elephant Zoo-FISH study delineates new chromosomal traits which link the two Afrotherian species phylogenetically. In the absence of any morphological evidence the chromosome painting data offer the first non-DNA sequence support for an Afrotherian clade. The comparative human and elephant genome maps provide new insights into the karyotype organization of the proto-afrotherian, the ancestor of extant placental mammals, which most probably consisted of 2n=46 chromosomes.

Animals↗
PubMed2026

A Translocation within the Ogataea Species Complex Alters Local Subtelomeric Chromatin while Maintaining Overall Genome Organization.

Eukaryotic genomic DNA is packaged in the nucleus as chromatin - a DNA-protein aggregate regulating genome function, including transcription. Chromatin is classified as either active euchromatin or silent heterochromatin, with each marked by distinct histone post-translational modifications (PTMs). Chromatin composition also mediates genome organization, including how heterochromatin aggregates at the nuclear periphery while euchromatin localizes to the nucleus center. In fungi, heterochromatic loci cluster, including independent centromere and telomere clusters that form the Rabl chromosome conformation. However, it is unknown if chromatin composition and genome organization are conserved in closely related fungi, and how they are impacted by large-scale chromosomal rearrangements. Here, we examined differences in histone PTM deposition, gene expression, and genome organization in two yeast species from the order Pichiales, which diverged from the common ancestor shared with Saccharomyces cerevisiae more than 200 million years ago. We focused on Ogataea polymorpha, which is used for industrial protein production, and Ogataea haglerorum, an isolate of which harbors a translocation between chromosomes 1 and 6. We show that the enrichment of three activating PTMs - the trimethylation of lysine 4 of histone H3 (H3K4me3) and the acetylation of lysine 9 of histone H3 (H3K9ac) or lysine 16 of histone H4 (H4K16ac) - are similar genome-wide yet individual gene orthologs have distinct chromatin and expression patterns. While both Ogataea genomes organize into a Rabl conformation, the O. haglerorum translocation alters subtelomeric chromatin composition and expression of genes affected by the translocation. Our work highlights the genome function differences that occur on a microevolutionary scale.

Ogataea↗
PubMed2026

A translocation within the Ogataea species complex alters local subtelomeric chromatin while maintaining overall genome organization.

Eukaryotic genomic DNA is packaged in the nucleus as chromatin-a DNA-protein aggregate regulating genome function, including transcription. Chromatin is classified as either active euchromatin or silent heterochromatin, with each marked by distinct histone post-translational modifications (PTMs). Chromatin composition also mediates genome organization, including how heterochromatin aggregates at the nuclear periphery while euchromatin localizes to the nucleus center. In fungi, heterochromatic loci cluster, including independent centromere and telomere clusters that form the Rabl chromosome conformation. However, it is unknown if chromatin composition and genome organization are conserved in closely related fungi, and how these features are impacted by large-scale chromosomal rearrangements. Here, we examined differences in histone PTM deposition, gene expression, and genome organization in 2 yeast species from the order Pichiales, which diverged from the common ancestor shared with Saccharomyces cerevisiae more than 200 million years ago. We focused on Ogataea polymorpha, which is used for industrial protein production, and Ogataea haglerorum, an isolate of which harbors a translocation between chromosomes 1 and 6. We show that the enrichment of 3 activating PTMs-the trimethylation of lysine 4 of histone H3 (H3K4me3) and the acetylation of lysine 9 of histone H3 (H3K9ac) or lysine 16 of histone H4 (H4K16ac)-are similar genome-wide, yet gene orthologs have distinct chromatin and expression patterns. While both Ogataea genomes organize into a Rabl conformation, the O. haglerorum translocation alters subtelomeric chromatin composition and expression of genes affected by the translocation. Our work highlights the genome function differences that occur on a microevolutionary scale.

Genome, Fungal↗
PubMed1999

Domain organization, genomic structure, evolution, and regulation of expression of the aggrecan gene family.

Proteoglycans are complex macromolecules, consisting of a polypeptide backbone to which are covalently attached one or more glycosaminoglycan chains. Molecular cloning has allowed identification of the genes encoding the core proteins of various proteoglycans, leading to a better understanding of the diversity of proteoglycan structure and function, as well as to the evolution of a classification of proteoglycans on the basis of emerging gene families that encode the different core proteins. One such family includes several proteoglycans that have been grouped with aggrecan, the large aggregating chondroitin sulfate proteoglycan of cartilage, based on a high number of sequence similarities within the N- and C-terminal domains. Thus far these proteoglycans include versican, neurocan, and brevican. It is now apparent that these proteins, as a group, are truly a gene family with shared structural motifs on the protein and nucleotide (mRNA) levels, and with nearly identical genomic organizations. Clearly a common ancestral origin is indicated for the members of the aggrecan family of proteoglycans. However, differing patterns of amplification and divergence have also occurred within certain exons across species and family members, leading to the class-characteristic protein motifs in the central carbohydrate-rich region exclusively. Thus the overall domain organization strongly suggests that sequence conservation in the terminal globular domains underlies common functions, whereas differences in the central portions of the genes account for functional specialization among the members of this gene family.

Aggrecans↗
PubMed1989

Genomic organization and sequences of immunoglobulin light chain genes in a primitive vertebrate suggest coevolution of immunoglobulin gene organization.

The genomic organization and sequence of immunoglobulin light chain genes in Heterodontus francisci (horned shark), a phylogenetically primitive vertebrate, have been characterized. Light chain variable (VL) and joining (JI) segments are separated by 380 nucleotides and together with the single constant region exon (CI), occupy less than 2.7 kb, the closest linkage described thus far for a rearranging gene system. The VL segment is flanked by a characteristic recombination signal sequence possessing a 12 nucleotide spacer; the recombination signal sequence flanking the JL segment is 23 nucleotides. The VL genes, unlike heavy chain genes, possess a typical upstream regulatory octamer as well as conserved enhancer core sequences in the intervening sequence separating JL and CL. Restriction mapping and genomic Southern blotting are consistent with the presence of multiple light chain gene clusters. There appear to be considerably fewer light than heavy chain genes. Heavy and light chain clusters show no evidence of genomic linkage using field inversion gel electrophoresis. The findings of major differences in the organization and functional rearrangement properties of immunoglobulin genes in species representing different levels of vertebrate evolution, but consistent similarity in the organization of heavy and light chain genes within a species, suggests that these systems may be coevolving.

Amino Acid Sequence↗
PubMed2000

Genomic organization and transcriptional regulation of the mouse GD3 synthase gene (ST8Sia I): comparison of genomic organization of the mouse sialyltransferase genes.

The genomic organization of the gene encoding the mouse GD3 synthase (ST8Sia I) has been determined. The mouse ST8Sia I gene spans over 100 kilobases of genomic DNA with a unique genomic structure of 5 exons. Analysis of the sequence immediately upstream of the transcription initiation site revealed that the ST8Sia I promoter contained no canonical TATA- or CCAAT-box, but contained a putative Sp1 binding site. Transient transfection experiments demonstrated functional promoter activity of the ST8Sia I promoter in an ST8Sia I-expressing cell line, P19, but not in an ST8Sia I-nonexpressing cell line, NIH3T3. Mobility shift assay and mutation analysis of the promoter region indicated that the Sp1 binding site is involved in the transcriptional regulation of the ST8Sia I gene in P19 cells. Here, the genomic structural analyses of mouse sialyltransferase genes are summarized and the genomic structures of these genes are compared.

Animals↗
PubMed1996

Human papillomavirus type 70 genome cloned from overlapping PCR products: complete nucleotide sequence and genomic organization.

The genome of human papillomavirus (HPV) type 70 (HPV 70), isolated from a cervical condyloma, was obtained by cloning overlapping PCR products. By automated DNA sequence analysis, the genome was found to consist of 7,905 bp with a G + C content of 40%. The genomic organization showed the characteristic features shared by other sequenced HPVs. Nucleotide sequence comparison with previously known HPV types demonstrated the closest homology with HPV 68 (82%), HPV 39 (82%), HPV 18 (70%), HPV 45 (70%), and HPV 59 (70%). Comparison with seven other partially sequenced HPV 70 isolates showed homologies of between 100 and 99.5%. Cloning of overlapping PCR products and automated DNA sequence analysis was found to be a feasible method of obtaining full-length sequences of HPVs.

Base Composition↗
PubMed2002

Rice genome organization: the centromere and genome interactions.

Over the last decade, many varied resources have become available for genome studies in rice. These resources include over 4000 DNA markers, several bacterial artificial chromosome (BAC) libraries, P-1 derived artificial chromosome (PAC) libraries and yeast artificial chromosome (YAC) libraries (genomic DNA clones, filters and end-sequences), retrotransposon tagged lines, and many chemical and irradiated mutant lines. Based on these, high-density genetic maps, cereal comparative maps, YAC and BAC physical maps, and quantitative trait loci (QTL) maps have been constructed, and 93 % of the genome has also been sequenced. These data have revealed key features of the genetic and physical structure of the rice genome and of the evolution of cereal chromosomes. This Botanical Briefing examines aspects of how the rice genome is organized structurally, functionally and evolutionarily. Emphasis is placed on the rice centromere, which is composed of long arrays of centromere-specific repetitive sequences. Differences and similarities amongst various cereal centromeres are detailed. These indicate essential features of centromere function. Another view of various kinds of interactive relationships within and between genomes, which could play crucial roles in genome organization and evolution, is also introduced. Constructed genetic and physical maps indicate duplication of chromosomal segments and spatial association between specific chromosome regions. A genome-wide survey of interactive genetic loci has identified various reproductive barriers that may drive speciation of the rice genome. The significance of these findings in genome organization and evolution is discussed.

Centromere↗
PubMed2025

Using Chromosome Conformation Capture Combined with Deep Sequencing (Hi-C) to Study Genome Organization in Bacteria.

Genome organization is fundamental to all living organisms. Long DNA molecules are organized in hierarchical orders to be accommodated into eukaryotic nuclei or bacterial cells, which are thousands of folds shorter. Over the past two decades, chromosome conformation capture (3C) techniques substantially advanced our understanding of genome folding inside cells. 3C involves crosslinking and proximity ligation, and quantifies the physical contacts between two DNA regions within the genome. Coupled with high-throughput sequencing, 3C-seq and Hi-C techniques detect genome-wide DNA interactions, providing a comprehensive view of global genome organization. Here, we describe a detailed method to prepare Hi-C libraries using Bacillus subtilis, which includes procedures of crosslinking chromatin, digesting the crosslinked genome, labeling DNA ends with biotin, ligating DNA, and preparing the DNA library for sequencing using an Illumina platform.

High-Throughput Nucleotide Sequencing↗
PubMed2004

Spatial genome organization during T-cell differentiation.

The spatial organization of genomes within the mammalian cell nucleus is non-random. The functional relevance of spatial genome organization might be in influencing gene expression programs as cells undergo changes during development and differentiation. To gain insight into the plasticity of genomes in space and time and to correlate the activity of specific genes with their nuclear position, we systematically analyzed the spatial genome organization in differentiating mouse T-cells. We find significant global reorganization of centromeres, chromosomes and gene loci during the differentiation process. Centromeres were repositioned from a preferentially internal distribution in undifferentiated cells to a preferentially peripheral position in differentiated CD4+ and CD8+ cells. Chromosome 6, containing the differentially expressed T-cell markers CD4 and CD8, underwent differential changes in position depending on whether cells differentiated into CD4+ or CD8+ thymocytes. Similarly, the two marker loci CD4 and CD8 showed distinct behavior in their position relative to the chromosome 6 centromere at various stages of differentiation. Our results demonstrate that significant spatial genome reorganization occurs during differentiation and indicate that the relationship between dynamic genome topology and single gene regulation is highly complex.

Animals↗
PubMed2006

A role for TFIIIC transcription factor complex in genome organization.

Eukaryotic genome complexity necessitates boundary and insulator elements to partition genomic content into distinct domains. We show that inverted repeat (IR) boundary elements flanking the fission yeast mating-type heterochromatin domain contain B-box sequences, which prevent heterochromatin from spreading into neighboring euchromatic regions by recruiting transcription factor TFIIIC complex without RNA polymerase III (Pol III). Genome-wide analysis reveals TFIIIC with Pol III at all tRNA genes, many of which cluster at pericentromeric heterochromatin domain boundaries. However, a single tRNA(phe) gene with modest TFIIIC enrichment is insufficient to serve as boundary and requires RNAi-associated element to restrain heterochromatin spreading. Remarkably, we found TFIIIC localization without Pol III at many sites located between divergent promoters. These sites appear to act as chromosome-organizing clamps by tethering distant loci to the nuclear periphery, at which TFIIIC is concentrated into several distinct bodies. Our analyses uncover a general genome organization mechanism involving conserved TFIIIC complex.

Chromosomes↗
PubMed2000

Genome organization in dicots: genome duplication in Arabidopsis and synteny between soybean and Arabidopsis.

Synteny between soybean and Arabidopsis was studied by using conceptual translations of DNA sequences from loci that map to soybean linkage groups A2, J, and L. Synteny was found between these linkage groups and all four of the Arabidopsis chromosomes, where GenBank contained enough sequence for synteny to be identified confidently. Soybean linkage group A2 (soyA2) and Arabidopsis chromosome I showed significant synteny over almost their entire lengths, with only 2-3 chromosomal rearrangements required to bring the maps into substantial agreement. Smaller blocks of synteny were identified between soyA2 and Arabidopsis chromosomes IV and V (near the RPP5 and RPP8 genes) and between soyA2 and Arabidopsis chromosomes I and V (near the PhyA and PhyC genes). These subchromosomal syntenic regions were themselves homeologous, suggesting that Arabidopsis has undergone a number of segmental duplications or possibly a complete genome duplication during its evolution. Homologies between the homeologous soybean linkage groups J and L and Arabidopsis chromosomes II and IV also revealed evidence of segmental duplication in Arabidopsis. Further support for this hypothesis was provided by the observation of very close linkage in Arabidopsis of homologs of soybean Vsp27 and Bng181 (three locations) and purple acid phosphatase-like sequences and homologs of soybean A256 (five locations). Simulations show that the synteny and duplications we report are unlikely to have arisen by chance during our analysis of the homology reports.

Acid Phosphatase↗
PubMed2004

Spatial genome organization.

The linear sequence of genomes exists within the three-dimensional space of the cell nucleus. The spatial arrangement of genes and chromosomes within the interphase nucleus is nonrandom and gives rise to specific patterns. While recent work has begun to describe some of the positioning patterns of chromosomes and gene loci, the structural constraints that are responsible for nonrandom positioning and the relevance of spatial genome organization for genome expression are unclear. Here we discuss potential functional consequences of spatial genome organization and we speculate on the possible molecular mechanisms of how genomes are organized within the space of the mammalian cell nucleus.

Animals↗
PubMed1999

Sequence of the genomic RNA of nudaurelia beta virus (Tetraviridae) defines a novel virus genome organization.

The monopartite genome of Nudaurelia beta virus, the type species of the Betatetravirus genus of the family Tetraviridae, consists of a single-stranded positive-sense RNA (ss+RNA) of 6625 nucleotides containing two open reading frames (ORFs). The 5' proximal ORF of 5778 nucleotides encodes a protein of 215 kDa containing three functional domains characteristic of RNA-dependent RNA polymerases of ss+RNA viruses. The 3' proximal ORF of 1836 nucleotides, which encodes the 66-kDa capsid precursor protein, overlaps the replicase gene by more than 99% (1827 nucleotides) and is in the +1 reading frame relative to the replicase reading frame. This capsid precursor is expressed via a 2656-nucleotide subgenomic RNA. The 3' terminus of the genome can be folded into a tRNA-like secondary structure that has a valine anticodon; the tRNA-like structure lacks a pseudoknot in the aminoacyl stem, a feature common to both genera of tetraviruses. Comparison of the sequences of Nudaurelia beta virus and another member of the Tetraviridae, Helicoverpa armigera stunt virus, which is in the genus Omegatetravirus, shows identities of 31.6% for the replicase and 24.5% for the capsid protein. The viruses in the genera Betatetravirus and Omegatetravirus of the Tetraviridae are clearly related but show significant differences in their genome organization. It is concluded that the ancestral virus with a bipartite genome, as found in the genus Omegatetravirus, likely evolved from a virus with an unsegmented genome, as found in the genus Betatetravirus, through evolution of the subgenomic RNA into a separate genomic component, with the accompanying loss of the capsid gene from the longer genomic RNA.

Amino Acid Sequence↗
PubMed2003

Comparative genomic organization of the cbl genes.

The genomic organization of cbl genes from a variety of mammalian and non-mammalian species was determined by a combination of cloning and database searches. Humans and mice have three cbl genes (c-cbl,(1) cblb, and cblc) which show remarkable conservation of the intron/exon structure over the region of the genes which encode the highly conserved N-terminal region of the proteins including the RING finger. Searches of genomic, cDNA, and EST databases revealed that one or more cbl genes exist in chordates, insects, and worms. Comparison of the complexity and genomic organization of the cbl gene family and the predicted Cbl proteins from various species suggests that the three mammalian cbl genes arose by two duplications of an ancestral gene. The genomic organization of the cbl genes from various species provides insight into the evolution of the cbl gene family.

Amino Acid Sequence↗