High-Resolution Whole-Genome Sequencing Reveals That Specific Chromatin Domains from Most Human Chromosomes Associate with Nucleoli

Abstract

We present a genomewide, high-resolution study of nucleolar-associated chromatin using comparative genome hybridization, deep sequencing, and photoactivation microscopy. We show specific regions from most chromosomes associate with nucleoli. These regions are AT-rich, enriched in repressed genes, and overlap with nuclear lamina-associated loci.

Functional redundancy in the nuclear compartmentalization of the late-replicating genome

“…In addition to containing the active and inactive rDNA repeats, nucleoli also associate with numerous specific sequences, including satellite repeats, zinc finger proteins, olfactory receptor genes, as well as members of the defensin and Ig gene families. 27,28 These identified nucleolar-associated regions encompassed about 4% of the genome and strongly correlate with low gene density and general transcriptional repression in the tissues examined. Moreover, due to the linear proximity of centromeres to NORs, PCH often colocalizes with PNH.…”

“…For example, labeled nucleolar chromatin has been shown to localize to either PH or PNH following mitosis, and localization of labeled LADs to either the periphery or nucleoli in the next cell cycle was shown to be stochastic and thus interchangeable. 27,34 The relationship between the 3 repressive subcompartments and gene loci associated with them is summarized in Figure 5, illustrating that repressed loci can reside at either PNH or PH and apparently relocalize between them. This may happen to a limited extent during G1, for example upon the functional disruption of nucleoli, but also upon nucleolar reformation and chromosomal decondensation following mitosis.…”

Nuclear organization during in vitro differentiation of porcine mesenchymal stem cells (MSCs) into adipocytes

“…Various nuclear components such as chromosome territories, subnuclear compartments, or the nuclear envelope contribute to the regulation of gene expression and other cellular functions (Pombo and Dillon 2015). There are many examples showing the relationship between 3D nuclear architecture and the transcriptional status of genes or chromatin domains, including radial positioning of gene-poor and gene-rich chromosome territories towards the nuclear periphery or interior, respectively (Bolzer et al 2005;Boyle et al 2001), localization of active/inactive loci within the chromosome territories (Chambeyron and Bickmore 2004;Volpi et al 2000), spatial clustering of co-regulated genes (Clowney et al 2012;Schoenfelder et al 2010), clustering of active genes at nuclear speckles or transcription factories (Brown et al 2008;Osborne et al 2004;Papantonis and Cook 2013), and association of transcriptionally inactive DNA regions with the nuclear lamina, nucleolus, or peri-centromeric heterochromatin (Finlan et al 2008;Reddy et al 2008;van Koningsbruggen et al 2010;Wijchers et al 2015).…”

Management of rRNA Transcription Activity in a Human Genome

“…Furthermore, it was found that stimulispecific rIGS loci, and breakpoint-enriched loci are surrounded by analogous repetitive elements (microsatellites, simple sequences, and fragments of Alu elements). It should be recalled here that many repetitive DNA sequences tend to form nucleoliassociated domains in human cells [30]. These results let us to propose that when chromosomal regions saturated by repetitive DNA sequences are brought close to the nucleolus envelope, they can meet rIGS loci producing ncRNAs.…”