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Giorgio Bernardi - One of the best experts on this subject based on the ideXlab platform.
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An Isochore Framework Underlies Chromatin Architecture.
PloS one, 2017Co-Authors: Kamel Jabbari, Giorgio BernardiAbstract:A recent investigation showed the existence of correlations between the architectural features of mammalian interphase chromosomes and the compositional properties of Isochores. This result prompted us to compare maps of the Topologically Associating Domains (TADs) and of the Lamina Associated Domains (LADs) with the corresponding Isochore maps of mouse and human chromosomes. This approach revealed that: 1) TADs and LADs correspond to Isochores, i.e., Isochores are the genomic units that underlie chromatin domains; 2) the conservation of TADs and LADs in mammalian genomes is explained by the evolutionary conservation of Isochores; 3) chromatin domains corresponding to GC-poor Isochores (e.g., LADs) show not only self-interactions but also intrachromosomal interactions with other domains also corresponding to GC-poor Isochores even if located far away; in contrast, chromatin domains corresponding to GC-rich Isochores (e.g., TADs) show more localized chromosomal interactions, many of which are inter-chromosomal. In conclusion, this investigation establishes a link between DNA sequences and chromatin architecture, explains the evolutionary conservation of TADs and LADs and provides new information on the spatial distribution of GC-poor/gene-poor and GC-rich/gene-rich chromosomal regions in the interphase nucleus.
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Heat map of chromatin interactions and Isochores map of mouse chromosome 17.
2017Co-Authors: Kamel Jabbari, Giorgio BernardiAbstract:(A). The heat map of chromatin interactions in mouse chromosome 17 (from [8]) is compared with the corresponding compositional profile (drawn from mm 10 genome assembly using a sliding window of 300 Kb and the program of [24]). Isochore families L1 to H3, characterized by increasing GC levels are defined according to the “fixed” boundaries between Isochore families (see Table A in S1 File) and are represented in different colors, deep blue, light blue, yellow, orange and red, respectively; the multicolored vertical bars on the top right indicate GC levels that correspond to the compositional boundaries among Isochore families. The self-interactions along the diagonal, as well as the interactions along the two major axes, correspond to short Isochore blocks or to individual Isochores, as stressed by lines through the coinciding boundaries of TADs (blue and broken black lines correspond to GC-poor and GC-rich Isochores or Isochore blocks, respectively; not all lines were drawn to avoid readability problems). Interactions corresponding to GC-poor regions are also seen in domains corresponding to other GC-poor regions even when located far away on the chromosomes, the intensity of such interactions decreasing, however, with distance. In the case of interactions corresponding to GC-rich Isochores, much weaker signals are present outside the diagonal, an indication of more localized interactions. Note that mouse chromosome 17 is an acrocentric chromosome and that the centromeric sequences correspond to the region near the origin of the Megabase (Mb) scale. Unless otherwise stated, all the interaction maps presented in this article are shown at a 250 Kb resolution and Isochores are visualized using a 300 Kb sliding window across chromosomes. (B) The heat map of mouse chromosome 17 is compared at a resolution of 100 Kb with the corresponding Isochore profile. Interactions along the diagonal are weaker because split into smaller domains, that reveal fine details. For example, the largest GC-rich region on the chromosome (around 30 Mb) is now resolved into several domains that present a finer correspondence with Isochores.
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Chromatin loops and Isochores from a 2.1 Mb region of human chromosome 20.
2017Co-Authors: Kamel Jabbari, Giorgio BernardiAbstract:The chromatin loops from a 2.1 Mb region of human chromosome 20 (Fig 6F from [3]) have been aligned with the corresponding heat map which was used to segment the corresponding DNA sequence into Isochores. In this Figure the “extended” Isochore ranges of Table A in S1 File were used to assign Isochores to families, in order to take care of some minimal trespassings of the 46% GC upper threshold of H1 Isochores. Asterisks indicate anomalies in the Isochores/domains correspondence (see Text).
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Chromatin domains are encoded and molded by Isochores: Isochores encode chromatin domains and chromosome compartments
2016Co-Authors: Giorgio BernardiAbstract:Abstract The formation of mammalian chromatin domains was investigated by analyzing the domain/Isochore connection. This showed that LADs correspond to GC-poor Isochores and are compositionally flat, flexible chromatin structures because of the local nucleosome depletions associated with the presence of oligo-A’s. In contrast, TADs correspond to GC-rich Isochores that consist of single or (much more frequently) multiple, GC peaks that shape the single or multiple, loops of TADs. Indeed, the increasing nucleosome depletions linked to the GC gradients of Isochore peaks lead to an increasing chromatin flexibility (accompanied by an increasing accessibility and decreasing supercoiling). In conclusion, Isochores not only encode but also mold chromatin architecture; while architectural proteins play a role in closing and insulating TAD loops. An extension of this model concerns the encoding of open and closed chromosome compartments by alternating GC-rich and GC-poor Isochores, the interactions among compartments defining the 3-D chromosome folding.
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The Anolis Lizard Genome: An Amniote Genome without Isochores?
Genome biology and evolution, 2016Co-Authors: Maria Costantini, Gonzalo Greif, Fernando Alvarez-valin, Giorgio BernardiAbstract:Two articles published 5 years ago concluded that the genome of the lizard Anolis carolinensis is an amniote genome without Isochores. This claim was apparently contradicting previous results on the general presence of an Isochore organization in all vertebrate genomes tested (including Anolis). In this investigation, we demonstrate that the Anolis genome is indeed heterogeneous in base composition, since its macrochromosomes comprise Isochores mainly from the L2 and H1 families (a moderately GC-poor and a moderately GC-rich family, respectively), and since the majority of the sequenced microchromosomes consists of H1 Isochores. These families are associated with different features of genome structure, including gene density and compositional correlations (e.g., GC3 vs flanking sequence GC and intron GC), as in the case of mammalian and avian genomes. Moreover, the assembled Anolis chromosomes have an enormous number of gaps, which could be due to sequencing problems in GC-rich regions of the genome. In conclusion, the Anolis genome is no exception to the general rule of an Isochore organization in the genomes of vertebrates (and other eukaryotes).
Maria Costantini - One of the best experts on this subject based on the ideXlab platform.
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The Isochores as a Fundamental Level of Genome Structure and Organization: A General Overview
Journal of Molecular Evolution, 2017Co-Authors: Maria Costantini, Héctor MustoAbstract:The recent availability of a number of fully sequenced genomes (including marine organisms) allowed to map very precisely the Isochores, based on DNA sequences, confirming the results obtained before genome sequencing by the ultracentrifugation in CsCl. In fact, the analytical profile of human DNA showed that the vertebrate genome is a mosaic of Isochores, typically megabase-size DNA segments that belong to a small number of families characterized by different GC levels. In this review, we will concentrate on some general genome features regarding the compositional organization from different organisms and their evolution, ranging from vertebrates to invertebrates until unicellular organisms. Since Isochores are tightly linked to biological properties such as gene density, replication timing, and recombination, the new level of detail provided by the Isochore map helped the understanding of genome structure, function, and evolution. All the findings reported here confirm the idea that the Isochores can be considered as a “fundamental level of genome structure and organization.” We stress that we do not discuss in this review the origin of Isochores, which is still a matter of controversy, but we focus on well established structural and physiological aspects.
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The Anolis Lizard Genome: An Amniote Genome without Isochores?
Genome biology and evolution, 2016Co-Authors: Maria Costantini, Gonzalo Greif, Fernando Alvarez-valin, Giorgio BernardiAbstract:Two articles published 5 years ago concluded that the genome of the lizard Anolis carolinensis is an amniote genome without Isochores. This claim was apparently contradicting previous results on the general presence of an Isochore organization in all vertebrate genomes tested (including Anolis). In this investigation, we demonstrate that the Anolis genome is indeed heterogeneous in base composition, since its macrochromosomes comprise Isochores mainly from the L2 and H1 families (a moderately GC-poor and a moderately GC-rich family, respectively), and since the majority of the sequenced microchromosomes consists of H1 Isochores. These families are associated with different features of genome structure, including gene density and compositional correlations (e.g., GC3 vs flanking sequence GC and intron GC), as in the case of mammalian and avian genomes. Moreover, the assembled Anolis chromosomes have an enormous number of gaps, which could be due to sequencing problems in GC-rich regions of the genome. In conclusion, the Anolis genome is no exception to the general rule of an Isochore organization in the genomes of vertebrates (and other eukaryotes).
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The Isochore patterns of invertebrate genomes
BMC Genomics, 2009Co-Authors: Rosalia Cammarano, Maria Costantini, Giorgio BernardiAbstract:Previous investigations from our laboratory were largely focused on the genome organization of vertebrates. We showed that these genomes are mosaics of Isochores, megabase-size DNA sequences that are fairly homogeneous in base composition yet belong to a small number of families that cover a wide compositional spectrum. A question raised by these results concerned how far back in evolution an Isochore organization of the eukaryotic genome arose. The present investigation deals with the compositional patterns of the invertebrates for which full genome sequences, or at least scaffolds, are available. We found that (i) a mosaic of Isochores is the long-range organization of all the genomes that we investigated; (ii) the Isochore families from the invertebrate genomes matched the corresponding families of vertebrates in GC levels; (iii) the relative amounts of Isochore families were remarkably different for different genomes, except for those from phylogenetically close species, such as the Drosophilids. This work demonstrates not only that an Isochore organization is present in all metazoan genomes analyzed that included Nematodes, Arthropods among Protostomia, Echinoderms and Chordates among Deuterostomia, but also that the Isochore families of invertebrates share GC levels with the corresponding families of vertebrates.
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The evolution of Isochore patterns in vertebrate genomes.
BMC genomics, 2009Co-Authors: Maria Costantini, Rosalia Cammarano, Giorgio BernardiAbstract:Previous work from our laboratory showed that (i) vertebrate genomes are mosaics of Isochores, typically megabase-size DNA segments that are fairly homogeneous in base composition; (ii) Isochores belong to a small number of families (five in the human genome) characterized by different GC levels; (iii) Isochore family patterns are different in fishes/amphibians and mammals/birds, the latter showing GC-rich Isochore families that are absent or very scarce in the former; (iv) there are two modes of genome evolution, a conservative one in which Isochore patterns basically do not change (e.g., among mammalian orders), and a transitional one, in which they do change (e.g., between amphibians and mammals); and (v) Isochores are tightly linked to a number of basic biological properties, such as gene density, gene expression, replication timing and recombination. The present availability of a number of fully sequenced genomes ranging from fishes to mammals allowed us to carry out investigations that (i) more precisely quantified our previous conclusions; (ii) showed that the different Isochore families of vertebrate genomes are largely conserved in GC levels and dinucleotide frequencies, as well as in Isochore size; and (iii) Isochore family patterns can be either conserved or change within both warm- and cold-blooded vertebrates. On the basis of the results presented, we propose that (i) the large conservation of GC levels and dinucleotide frequencies may reflect the conservation of chromatin structures; (ii) the conservation of Isochore size may be linked to the role played by Isochores in chromosome structure and replication; (iii) the formation, the maintainance and the changes of Isochore patterns are due to natural selection.
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The short-sequence designs of Isochores from the human genome.
Proceedings of the National Academy of Sciences of the United States of America, 2008Co-Authors: Maria Costantini, Giorgio BernardiAbstract:The human genome, a typical mammalian genome, is made up of long (≈1-Mb, on average) regions, the Isochores, that are fairly homogeneous in base composition and belong in five families characterized by different GC levels. An analysis of di- and tri-nucleotide densities in the Isochores from the five families has shown large differences. These different “short-sequence designs:” (i) account for the fractionation of human DNA (and vertebrate DNA in general) when using sequence-specific ligands in density gradients, (ii) are very similar in whole Isochores and in the corresponding intergenic sequences and introns, (iii) are reflected in different codon usages, (iv) lead to amino acid differences that increase the thermal stability of the proteins encoded by genes located in increasingly GC-rich Isochore families, and (v) correspond to different chromatin structures.
A. Frennet - One of the best experts on this subject based on the ideXlab platform.
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Thermodynamic parameters of H_2 adsorption as criteria to characterize silica-supported palladium catalyst
Catalysis Letters, 1997Co-Authors: S. Decker, A. FrennetAbstract:The thermodynamics of hydrogen adsorption on palladium catalyst supported on silica is determined by isosteric analysis of series of Isochores measured by the volumetric method. The variations of this thermodynamics (ΔH, ΔS) with adsorbed amount allows the discrimination between the different hydrogen species present on such a catalyst (hydrogen strongly and weakly chemisorbed on the palladium, absorbed in the palladium particles and molecularly adsorbed on the support). Namely, the variations of only the heat of adsorption with adsorbed amount allow the determination of hydride and weakly adsorbed hydrogen species. It is shown that these amounts can even be determined from one single Isochore.
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Thermodynamic parameters of H2 adsorption as criteria to characterize silica-supported palladium catalyst
Catalysis Letters, 1997Co-Authors: S. Decker, A. FrennetAbstract:The thermodynamics of hydrogen adsorption on palladium catalyst supported on silica is determined by isosteric analysis of series of Isochores measured by the volumetric method. The variations of this thermodynamics (ΔH, ΔS) with adsorbed amount allows the discrimination between the different hydrogen species present on such a catalyst (hydrogen strongly and weakly chemisorbed on the palladium, absorbed in the palladium particles and molecularly adsorbed on the support). Namely, the variations of only the heat of adsorption with adsorbed amount allow the determination of hydride and weakly adsorbed hydrogen species. It is shown that these amounts can even be determined from one single Isochore.
S. Decker - One of the best experts on this subject based on the ideXlab platform.
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Thermodynamic parameters of H_2 adsorption as criteria to characterize silica-supported palladium catalyst
Catalysis Letters, 1997Co-Authors: S. Decker, A. FrennetAbstract:The thermodynamics of hydrogen adsorption on palladium catalyst supported on silica is determined by isosteric analysis of series of Isochores measured by the volumetric method. The variations of this thermodynamics (ΔH, ΔS) with adsorbed amount allows the discrimination between the different hydrogen species present on such a catalyst (hydrogen strongly and weakly chemisorbed on the palladium, absorbed in the palladium particles and molecularly adsorbed on the support). Namely, the variations of only the heat of adsorption with adsorbed amount allow the determination of hydride and weakly adsorbed hydrogen species. It is shown that these amounts can even be determined from one single Isochore.
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Thermodynamic parameters of H2 adsorption as criteria to characterize silica-supported palladium catalyst
Catalysis Letters, 1997Co-Authors: S. Decker, A. FrennetAbstract:The thermodynamics of hydrogen adsorption on palladium catalyst supported on silica is determined by isosteric analysis of series of Isochores measured by the volumetric method. The variations of this thermodynamics (ΔH, ΔS) with adsorbed amount allows the discrimination between the different hydrogen species present on such a catalyst (hydrogen strongly and weakly chemisorbed on the palladium, absorbed in the palladium particles and molecularly adsorbed on the support). Namely, the variations of only the heat of adsorption with adsorbed amount allow the determination of hydride and weakly adsorbed hydrogen species. It is shown that these amounts can even be determined from one single Isochore.
José L. Oliver - One of the best experts on this subject based on the ideXlab platform.
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The biased distribution of Alus in human Isochores might be driven by recombination.
Journal of molecular evolution, 2005Co-Authors: Michael Hackenberg, Pedro Carpena, Pedro Bernaola-galván, José L. OliverAbstract:Alu retrotransposons do not show a homogeneous distribution over the human genome but have a higher density in GC-rich (H) than in AT- rich (L) Isochores. However, since they preferentially insert into the L Isochores, the question arises: What is the evolutionary mechanism that shifts the Alu density maximum from L to H Isochores? To disclose the role played by each of the potential mechanisms involved in such biased distribution, we carried out a genome-wide analysis of the density of the Alus as a function of their evolutionary age, Isochore mem- bership, and intron vs. intergene location. Since Alus depend on the retrotransposase encoded by the LINE1 elements, we also studied the distribution of LINE1 to provide a complete evolutionary scenario. We consecutively check, and discard, the contribu- tions of the Alu/LINE1 competition for retrotrans- posase, compositional matching pressure, and Alu overrepresentation in introns. In analyzing the role played by unequal recombination, we scan the gen- ome for Alu trimers, a direct product of Alu-Alu recombination. Through computer simulations, we show that such trimers are much more frequent than expected, the observed/expected ratio being higher in L than in H Isochores. This result, together with the known higher selective disadvantage of recombina- tion products in H Isochores, points to Alu-Alu recombination as the main agent provoking the density shift of Alus toward the GC-rich parts of the genome. Two independent pieces of evidence—the lower evolutionary divergence shown by recently in- serted Alu subfamilies and the higher frequency of old stand-alone Alus in L Isochores—support such a conclusion. Other evolutionary factors, such as pop- ulation bottlenecks during primate speciation, may have accelerated the fast accumulation of Alus in GC-rich Isochores.
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IsoFinder: computational prediction of Isochores in genome sequences.
Nucleic acids research, 2004Co-Authors: José L. Oliver, Pedro Carpena, Michael Hackenberg, Pedro Bernaola-galvánAbstract:Isochores are long genome segments homogeneous in G+C. Here, we describe an algorithm (IsoFinder) running on the web (http://bioinfo2.ugr.es/IsoF/isofinder.html) able to predict Isochores at the sequence level. We move a sliding pointer from left to right along the DNA sequence. At each position of the pointer, we compute the mean G+C values to the left and to the right of the pointer. We then determine the position of the pointer for which the difference between left and right mean values (as measured by the t-statistic) reaches its maximum. Next, we determine the statistical significance of this potential cutting point, after filtering out short-scale heterogeneities below 3 kb by applying a coarse-graining technique. Finally, the program checks whether this significance exceeds a probability threshold. If so, the sequence is cut at this point into two subsequences; otherwise, the sequence remains undivided. The procedure continues recursively for each of the two resulting subsequences created by each cut. This leads to the decomposition of a chromosome sequence into long homogeneous genome regions (LHGRs) with well-defined mean G+C contents, each significantly different from the G+C contents of the adjacent LHGRs. Most LHGRs can be identified with Bernardi's Isochores, given their correlation with biological features such as gene density, SINE and LINE (short, long interspersed repetitive elements) densities, recombination rate or single nucleotide polymorphism variability. The resulting Isochore maps are available at our web site (http://bioinfo2.ugr.es/Isochores/), and also at the UCSC Genome Browser (http://genome.cse.ucsc.edu/).
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Isochores merit the prefix 'iso'
Computational biology and chemistry, 2003Co-Authors: Pedro Bernaola-galván, Pedro Carpena, José L. OliverAbstract:The Isochore concept in the human genome sequence was challenged in an analysis by the International Human Genome Sequencing Consortium (IHGSC). We argue here that a statement in the IHGSC's analysis concerning the existence of Isochores is misleading, because the homogeneity was not examined at a large enough length scale and consequently an inappropriate statistical test was applied. A test of the existence of Isochores should be equivalent to a test of homogeneity or equality of windowed GC%. The statistical test applied in the IHGSC's analysis, the binomial test, is a test of whether individual bases are independent and identically-distributed (iid). For testing the existence of Isochores, or homogeneity in windowed GC%, we propose to use another statistical test: the analysis of variance (ANOVA). It can be shown that DNA sequences that are rejected by the binomial test may not be rejected by the ANOVA test.
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Isochore chromosome maps of the human genome.
Gene, 2002Co-Authors: José L. Oliver, Pedro Carpena, Ramón Román-roldán, Trinidad Mata-balaguer, Andrés Mejı́as-romero, Michael Hackenberg, Pedro Bernaola-galvánAbstract:The human genome is a mosaic of Isochores, which are long DNA segments (z.Gt;300 kbp) relatively homogeneous in G+C. Human Isochores were first identified by density-gradient ultracentrifugation of bulk DNA, and differ in important features, e.g. genes are found predominantly in the GC-richest Isochores. Here, we use a reliable segmentation method to partition the longest contigs in the human genome draft sequence into long homogeneous genome regions (LHGRs), thereby revealing the Isochore structure of the human genome. The advantages of the Isochore maps presented here are: (1) sequence heterogeneities at different scales are shown in the same plot; (2) pair-wise compositional differences between adjacent regions are all statistically significant; (3) Isochore boundaries are accurately defined to single base pair resolution; and (4) both gradual and abrupt Isochore boundaries are simultaneously revealed. Taking advantage of the wide sample of genome sequence analyzed, we investigate the correspondence between LHGRs and true human Isochores revealed through DNA centrifugation. LHGRs show many of the typical Isochore features, mainly size distribution, G+C range, and proportions of the Isochore classes. The relative density of genes, Alu and long interspersed nuclear element repeats and the different types of single nucleotide polymorphisms on LHGRs also coincide with expectations in true Isochores. Potential applications of Isochore maps range from the improvement of gene-finding algorithms to the prediction of linkage disequilibrium levels in association studies between marker genes and complex traits. The coordinates for the LHGRs identified in all the contigs longer than 2 Mb in the human genome sequence are available at the online resource on Isochore mapping: http://bioinfo2.ugr.es/Isochores.
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Isochores Merit the Prefix 'Iso'
Genome Biology, 2002Co-Authors: Pedro Bernaola-galván, Pedro Carpena, José L. OliverAbstract:The Isochore concept in human genome sequence was challenged in an analysis by the International Human Genome Sequencing Consortium (IHGSC). We argue here that a statement in IGHSC analysis concerning the existence of Isochore is incorrect, because it had applied an inappropriate statistical test. To test the existence of Isochores should be equivalent to a test of homogeneity of windowed GC%. The statistical test applied in the IHGSC's analysis, the binomial test, is however a test of a sequence being random on the base level. For testing the existence of Isochore, or homogeneity in GC%, we propose to use another statistical test: the analysis of variance (ANOVA). It can be shown that DNA sequences that are rejected by binomial test may not be rejected by the ANOVA test.
