High-resolution whole-genome sequencing reveals that specific chromatin domains from most human chromosomes associate with nucleoli.
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.
van Koningsbruggen
Silvana
S
Wellcome Trust Centre for Gene Regulation and Expression, College of Life Sciences, University of Dundee, Dundee DD1 5EH, United Kingdom.
Gierlinski
Marek
M
Schofield
Pietá
P
Martin
David
D
Barton
Geoffey J
GJ
Ariyurek
Yavuz
Y
den Dunnen
Johan T
JT
Lamond
Angus I
AI
D002453:Cell Cycle; D045744:Cell Line, Tumor; D002466:Cell Nucleolus / Q000000981:diagnostic imaging* / Q000235:genetics*; D002843:Chromatin / Q000235:genetics*; D002877:Chromosomes, Human / Q000235:genetics*; D055028:Comparative Genomic Hybridization; D019295:Computational Biology; D004275:DNA, Ribosomal / Q000378:metabolism; D005453:Fluorescence; D020459:Genes, rRNA; D055106:Genome-Wide Association Study / Q000379:methods; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D017403:In Situ Hybridization; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D059010:Single-Cell Analysis; D059008:Time-Lapse Imaging; D014463:Ultrasonography
D002843:Chromatin; D004275:DNA, Ribosomal
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