High-resolution whole-genome sequencing reveals that specific Chromatin Domains from most human chromosomes associate with nucleoli

Silvana van Koningsbruggen, Marek Gierlinski, Pieta Schofield, David Martin, Geoffrey J. Barton, Yavuz Ariyurek, Johan T. den Dunnen, Angus I. Lamond

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    177 Citations (Scopus)

    Abstract

    The nuclear space is mostly occupied by chromosome territories and nuclear bodies. Although this organization of chromosomes affects gene function, relatively little is known about the role of nuclear bodies in the organization of chromosomal regions. The nucleolus is the best-studied subnuclear structure and forms around the rRNA repeat gene clusters on the acrocentric chromosomes. In addition to rDNA, other chromatin sequences also surround the nucleolar surface and may even loop into the nucleolus. These additional nucleolar-associated domains (NADs) have not been well characterized. We present here a whole-genome, high-resolution analysis of chromatin endogenously associated with nucleoli. We have used a combination of three complementary approaches, namely fluorescence comparative genome hybridization, high-throughput deep DNA sequencing and photoactivation combined with time-lapse fluorescence microscopy. The data show that specific sequences from most human chromosomes, in addition to the rDNA repeat units, associate with nucleoli in a reproducible and heritable manner. NADs have in common a high density of AT-rich sequence elements, low gene density and a statistically significant enrichment in transcriptionally repressed genes. Unexpectedly, both the direct DNA sequencing and fluorescence photoactivation data show that certain chromatin loci can specifically associate with either the nucleolus, or the nuclear envelope.

    Original languageEnglish
    Pages (from-to)3735-3748
    Number of pages14
    JournalMolecular Biology of the Cell
    Volume21
    Issue number21
    DOIs
    Publication statusPublished - 1 Nov 2010

    Keywords

    • TELOMERIC DNA-SEQUENCES
    • GENE-REGULATION
    • COILED BODIES
    • CELL-CYCLE
    • SPATIAL-ORGANIZATION
    • LIVING CELLS
    • RNA GENES
    • TERRITORIES
    • LOCALIZATION
    • ARCHITECTURE

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