Unravelling global genome organization by 3C-seq

The Wistar Institute, Philadelphia, PA, USA.
Seminars in Cell and Developmental Biology (Impact Factor: 6.27). 11/2011; 23(2):213-21. DOI: 10.1016/j.semcdb.2011.11.003
Source: PubMed


Eukaryotic genomes exist in the cell nucleus as an elaborate three-dimensional structure which reflects various nuclear processes such as transcription, DNA replication and repair. Next-generation sequencing (NGS) combined with chromosome conformation capture (3C), referred to as 3C-seq in this article, has recently been applied to the yeast and human genomes, revealing genome-wide views of functional associations among genes and their regulatory elements. Here, we compare the latest genomic approaches such as 3C-seq and ChIA-PET, and provide a condensed overview of how eukaryotic genomes are functionally organized in the nucleus.

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    • "Genome organizations have been characterized in terms of several aspects, including chromosomal territories, nuclear bodies and genomic associations involving transcriptional regulatory elements and their target genes (Cremer and Cremer, 2010; Sexton et al., 2009; Tanizawa and Noma, 2012; Williams et al., 2010; Zhao et al., 2009). It is becoming clear that threedimensional (3D) genome organization is connected to various nuclear processes, such as transcription, DNA replication and repair, and chromatin domain formation (Cook, 1999; Labrador and Corces, 2002; Misteli, 2007). "
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    ABSTRACT: Dispersed genetic elements such as retrotransposons and Pol III-transcribed genes, including tRNA and 5S rRNA, cluster and associate with centromeres in fission yeast through the condensin function. However, the dynamics of these condensin-mediated genomic associations remains unknown. We have examined the 3D motions of genomic loci including the centromere, telomere, ribosomal DNA (rDNA) repeat locus, and the loci carrying Pol III-transcribed genes or LTR retrotransposons in live cells at as short as 1.5-sec intervals. Treatment with carbendazim (CBZ), a microtubule-destabilizing agent, not only prevents centromeric motion, but also reduces the mobility of the other genomic loci during interphase. Further analyses demonstrate that condensin-mediated associations between centromeres and the genomic loci are clonal, infrequent, and transient. However, when associated, centromeres and the genomic loci migrate together in a coordinated fashion. In addition, a condensin mutation that disrupts associations between centromeres and the genomic loci results in a concomitant decrease in the mobility of the loci. Our study suggests that highly mobile centromeres pulled by microtubules in cytoplasm serve as "genome mobility elements" by facilitating physical relocations of associating genomic regions.
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    • "The mammalian genome appears to have accommodated widespread repetitive elements by providing each chromosome a specific domain. However, in the more tightly packed yeast nucleus, individual chromosomes are in intimate contact, which could explain why yeast have a limited number of repetititve elements in its genome (Tanizawa and Noma, 2011; Duan et al., 2010; Figure 6A). For mammalian genomes, perhaps the positive functions provided by repetitive sequences (e.g. "
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    ABSTRACT: Repetitive DNA is present in the eukaryotic genome in the form of segmental duplications, tandem and interspersed repeats, and satellites. Repetitive sequences can be beneficial by serving specific cellular functions (e.g. centromeric and telomeric DNA) and by providing a rapid means for adaptive evolution. However, such elements are also substrates for deleterious chromosomal rearrangements that affect fitness and promote human disease. Recent studies analyzing the role of nuclear organization in DNA repair and factors that suppress non-allelic homologous recombination (NAHR) have provided insights into how genome stability is maintained in eukaryotes. In this review, we outline the types of repetitive sequences seen in eukaryotic genomes and how recombination mechanisms are regulated at the DNA sequence, cell organization, chromatin structure, and cell cycle control levels to prevent chromosomal rearrangements involving these sequences.
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