Pericentromeric heterochromatin is hierarchically organized and spatially contacts H3K9me2 islands in euchromatin.

Membraneless pericentromeric heterochromatin (PCH) domains play vital roles in chromosome dynamics and genome stability. However, our current understanding of 3D genome organization does not include PCH domains because of technical challenges associated with repetitive sequences enriched in PCH genomic regions. We investigated the 3D architecture of Drosophila melanogaster PCH domains and their spatial associations with the euchromatic genome by developing a novel analysis method that incorporates genome-wide Hi-C reads originating from PCH DNA. Combined with cytogenetic analysis, we reveal a hierarchical organization of the PCH domains into distinct territories. Strikingly, H3K9me2-enriched regions embedded in the euchromatic genome show prevalent 3D interactions with the PCH domain. These spatial contacts require H3K9me2 enrichment, are likely mediated by liquid-liquid phase separation, and may influence organismal fitness. Our findings have important implications for how PCH architecture influences the function and evolution of both repetitive heterochromatin and the gene-rich euchromatin

Uncovering Proximity of Chromosome Territories using Classical Algebraic Statistics

Exchange type chromosome aberrations (ETCAs) are rearrangements of the genome that occur when chromosomes break and the resulting fragments rejoin with other fragments from other chromosomes. ETCAs are commonly observed in cancer cells and in cells exposed to radiation. The frequency of these chromosome rearrangements is correlated with their spatial proximity, therefore it can be used to infer the three dimensional organization of the genome. Extracting statistical significance of spatial proximity from cancer and radiation data has remained somewhat elusive because of the sparsity of the data. We here propose a new approach to study the three dimensional organization of the genome using algebraic statistics. We test our method on a published data set of irradiated human blood lymphocyte cells. We provide a rigorous method for testing the overall organization of the genome, and in agreement with previous results we find a random relative positioning of chromosomes with the exception of the chromosome pairs \{1,22\} and \{13,14\} that have a significantly larger number of ETCAs than the rest of the chromosome pairs suggesting their spatial proximity. We conclude that algebraic methods can successfully be used to analyze genetic data and have potential applications to larger and more complex data sets

The amphioxus genome and the evolution of the chordate karyotype

Lancelets ('amphioxus') are the modern survivors of an ancient chordate lineage, with a fossil record dating back to the Cambrian period. Here we describe the structure and gene content of the highly polymorphic approx520-megabase genome of the Florida lancelet Branchiostoma floridae, and analyse it in the context of chordate evolution. Whole-genome comparisons illuminate the murky relationships among the three chordate groups (tunicates, lancelets and vertebrates), and allow not only reconstruction of the gene complement of the last common chordate ancestor but also partial reconstruction of its genomic organization, as well as a description of two genome-wide duplications and subsequent reorganizations in the vertebrate lineage. These genome-scale events shaped the vertebrate genome and provided additional genetic variation for exploitation during vertebrate evolution

The genome of the medieval Black Death agent (extended abstract)

The genome of a 650 year old Yersinia pestis bacteria, responsible for the medieval Black Death, was recently sequenced and assembled into 2,105 contigs from the main chromosome. According to the point mutation record, the medieval bacteria could be an ancestor of most Yersinia pestis extant species, which opens the way to reconstructing the organization of these contigs using a comparative approach. We show that recent computational paleogenomics methods, aiming at reconstructing the organization of ancestral genomes from the comparison of extant genomes, can be used to correct, order and complete the contig set of the Black Death agent genome, providing a full chromosome sequence, at the nucleotide scale, of this ancient bacteria. This sequence suggests that a burst of mobile elements insertions predated the Black Death, leading to an exceptional genome plasticity and increase in rearrangement rate.Comment: Extended abstract of a talk presented at the conference JOBIM 2013, https://colloque.inra.fr/jobim2013_eng/. Full paper submitte

Towards a robust algorithm to determine topological domains from colocalization data

One of the most important tasks in understanding the complex spatial organization of the genome consists in extracting information about this spatial organization, the function and structure of chromatin topological domains from existing experimental data, in particular, from genome colocalization (Hi-C) matrices. Here we present an algorithm allowing to reveal the underlying hierarchical domain structure of a polymer conformation from analyzing the modularity of colocalization matrices. We also test this algorithm on several model polymer structures: equilibrium globules, random fractal globules and regular fractal (Peano) conformations. We define what we call a spectrum of cluster borders, and show that these spectra behave strikingly differently for equilibrium and fractal conformations, allowing us to suggest an additional criterion to identify fractal polymer conformations

The CACTA transposon Bot1 played a major role in Brassica genome divergence and gene proliferation

We isolated and characterized a Brassica C genome-specific CACTA element, which was designated Bot1 (Brassica oleracea transposon 1). After analysing phylogenetic relationships, copy numbers and sequence similarity of Bot1 and Bot1 analogues in B. oleracea (C genome) versus Brassica rapa (A genome), we concluded that Bot1 has encountered several rounds of amplification in the oleracea genome only, and has played a major role in the recent rapa and oleracea genome divergence. We performed in silico analyses of the genomic organization and internal structure of Bot1, and established which segment of Bot1 is C-genome specific. Our work reports a fully characterized Brassica repetitive sequence that can distinguish the Brassica A and C chromosomes in the allotetraploid Brassica napus, by fluorescent in situ hybridization. We demonstrated that Bot1 carries a host S locus-associated SLL3 gene copy. We speculate that Bot1 was involved in the proliferation of SLL3 around the Brassica genome. The present study reinforces the assumption that transposons are a major driver of genome and gene evolution in higher plants

A biophysical approach to large-scale protein-DNA binding data

About this book * Cutting-edge genome analysis methods from leading bioinformaticians An accurate description of current scientific developments in the field of bioinformatics and computational implementation is presented by research of the BioSapiens Network of Excellence. Bioinformatics is essential for annotating the structure and function of genes, proteins and the analysis of complete genomes and to molecular biology and biochemistry. Included is an overview of bioinformatics, the full spectrum of genome annotation approaches including; genome analysis and gene prediction, gene regulation analysis and expression, genome variation and QTL analysis, large scale protein annotation of function and structure, annotation and prediction of protein interactions, and the organization and annotation of molecular networks and biochemical pathways. Also covered is a technical framework to organize and represent genome data using the DAS technology and work in the annotation of two large genomic sets: HIV/HCV viral genomes and splicing alternatives potentially encoded in 1% of the human genome

Genome Organization in Sponges

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Non-random chromosome positioning in mammalian sperm nuclei, with migration of the sex chromosomes during late spermatogenesis

Chromosomes are highly organized and compartmentalized in cell nuclei. The analysis of their position is a powerful way to monitor genome organization in different cell types and states. Evidence suggests that the organization of the genome could be functionally important for influencing different cellular and developmental processes, particularly at early stages of development (i.e. fertilization and the consequent entry of the sperm nucleus into the egg). The position of chromosomes in the sperm nucleus might be crucial, because their location could determine the time at which particular chromatin domains are decondensed and remodelled, allowing some epigenetic level of control or influence over subsequent paternal gene expression in the embryo. Here, we analyse genome organization by chromosome position in mammalian sperm nuclei from three breeds of pig, as a model species. We have mapped the preferential position of all chromosomes (bar one) in sperm nuclei in two dimensions and have established that the sex chromosomes are the most internally localized chromosomes in mature sperm. The distribution of two autosomes and chromosomes X and Y in sperm heads was compared in primary and secondary spermatocytes and spermatids in porcine testes. The sex chromosomes were found at the nuclear edge in primary spermatocytes, which correlates with the known position of the XY body and their position in somatic cells, whereas, in spermatids, the sex chromosomes were much more centrally located, mirroring the position of these chromosomes in ejaculated spermatozoa. This study reveals the temporal repositioning of chromosome territories in spermatogenesis