Meet the neighbours: tools to dissect nuclear structure and function

Osborne, Cameron S.; Ewels, Philip; Young, Alice N.C.

doi:10.1093/bfgp/elq034

Cited by 7 publications

(8 citation statements)

References 45 publications

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“…The advent of genome-wide proximity assays has enabled these questions to be addressed (39). The Alt group, along with Zhang and colleagues, has used Hi-C, an assay that captures a lowresolution snapshot of organization of the entire genome, to examine how is the genome arranged in cells that contain a nuclease recognition site, before the induction of doublestrand breaks (40).…”

Section: Proximity Transcription and Chromosomal Translocationsmentioning

confidence: 99%

Molecular Pathways: Transcription Factories and Chromosomal Translocations

Osborne

2014

Clinical Cancer Research

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The mammalian nucleus is a highly complex structure that carries out a diverse range of functions such as DNA replication, cell division, RNA processing, and nuclear export/import. Many of these activities occur at discrete subcompartments that intersect with specific regions of the genome. Over the past few decades, evidence has accumulated to suggest that RNA transcription also occurs in specialized sites, called transcription factories, that may influence how the genome is organized. There may be certain efficiency benefits to cluster transcriptional activity in this way. However, the clustering of genes at transcription factories may have consequences for genome stability, and increase the susceptibility to recurrent chromosomal translocations that lead to cancer. The relationships between genome organization, transcription, and chromosomal translocation formation will have important implications in understanding the causes of therapy-related cancers. Clin Cancer Res; 20(2); 296-300. Ó2013 AACR.

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Section: Proximity Transcription and Chromosomal Translocationsmentioning

confidence: 99%

Molecular Pathways: Transcription Factories and Chromosomal Translocations

Osborne

2014

Clinical Cancer Research

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“…Since its invention, interest in the application and improvement of the 3C approach has been ever increasing. New derivative high-resolution, high-throughput methods that enable us to study DNA–DNA contacts at a much larger scale are rapidly being developed (2). The number of available datasets employing the 4C (3,4), 5C (5), GCC (6) and particularly the Hi-C (7,8) and TCC (9) approaches is steadily on the rise.…”

Section: Introductionmentioning

confidence: 99%

A complex network framework for unbiased statistical analyses of DNA–DNA contact maps

Kruse

Sewitz

Babu

2012

Nucleic Acids Research

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Experimental techniques for the investigation of three-dimensional (3D) genome organization are being developed at a fast pace. Currently, the associated computational methods are mostly specific to the individual experimental approach. Here we present a general statistical framework that is widely applicable to the analysis of genomic contact maps, irrespective of the data acquisition and normalization processes. Within this framework DNA–DNA contact data are represented as a complex network, for which a broad number of directly applicable methods already exist. In such a network representation, DNA segments and contacts between them are denoted as nodes and edges, respectively. Furthermore, we present a robust method for generating randomized contact networks that explicitly take into account the inherent 3D nature of the genome and serve as realistic null-models for unbiased statistical analyses. By integrating a variety of large-scale genome-wide datasets we demonstrate that meiotic crossover sites display enriched genomic contacts and that cohesin-bound genes are significantly colocalized in the yeast nucleus. We anticipate that the complex network framework in conjunction with the randomization of DNA–DNA contact networks will become a widely used tool in the study of nuclear architecture.

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“…These extensions of the original 3C protocol allow a more unbiased, quantitative approach to determining interactions between a specific genomic site and sites throughout the genome. One innovation is the ligation of oligonucleotide linkers to immunoprecipitated fragments, followed by sequencing, to identify direct or indirect DNA contact sites of a given protein (Osborne, Ewels, & Young, 2011; Sanyal, Baù, Martí-Renom, & Dekker, 2011; van Steensel & Dekker, 2010). Much as ChIP-on-chip extended the range of the ChIP assay to a genomic scale, interactions between a given locus and the rest of the genome can be determined by 4C (either “circular chromosome conformation capture” or “chromosome conformation capture-on-chip”), which involves ligating a known segment of DNA to an array of purified 3C products, amplifying the resulting population of circular DNA molecules with inverse PCR, and analyzing the PCR products by high-throughput sequencing (Simonis et al, 2006; Würtele & Chartrand, 2006; Zhao et al, 2006).…”

Section: The Components Of Epigenetic Transcriptional Regulationmentioning

confidence: 99%

Epigenetic Control of Cytokine Gene Expression

Falvo

Jasenosky

Kruidenier

et al. 2013

Advances in Immunology

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Epigenetics encompasses transient and heritable modifications to DNA and nucleosomes in the native chromatin context. For example, enzymatic addition of chemical moieties to the N-terminal “tails” of histones, particularly acetylation and methylation of lysine residues in the histone tails of H3 and H4, plays a key role in regulation of gene transcription. The modified histones, which are physically associated with gene regulatory regions that typically occur within conserved noncoding sequences, play a functional role in active, poised, or repressed gene transcription. The “histone code” defined by these modifications, along with the chromatin-binding acetylases, deacetylases, methylases, demethylases, and other enzymes that direct modifications resulting in specific patterns of histone modification, shows considerable evolutionary conservation from yeast to humans. Direct modifications at the DNA level, such as cytosine methylation at CpG motifs that represses promoter activity, are another highly conserved epigenetic mechanism of gene regulation. Furthermore, epigenetic modifications at the nucleosome or DNA level can also be coupled with higher-order intra- or interchromosomal interactions that influence the location of regulatory elements and that can place them in an environment of specific nucleoprotein complexes associated with transcription. In the mammalian immune system, epigenetic gene regulation is a crucial mechanism for a range of physiological processes, including the innate host immune response to pathogens and T cell differentiation driven by specific patterns of cytokine gene expression. Here, we will review current findings regarding epigenetic regulation of cytokine genes important in innate and/or adaptive immune responses, with a special focus upon the tumor necrosis factor/lymphotoxin locus and cytokine-driven CD4+ T cell differentiation into the Th1, Th2, and Th17 lineages.

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Meet the neighbours: tools to dissect nuclear structure and function

Cited by 7 publications

References 45 publications

Molecular Pathways: Transcription Factories and Chromosomal Translocations

Molecular Pathways: Transcription Factories and Chromosomal Translocations

A complex network framework for unbiased statistical analyses of DNA–DNA contact maps

Epigenetic Control of Cytokine Gene Expression

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