DUNDEE_CLS:GRE:AIL:SvK_Study_1
Human Nucleoli associate with Specific Chromatin Domains  Containing Transcription-repressed Genes from Multiple Chromosomes
Nucleoli are subnuclear organelles whose major role is the transcription and processing of ribosomal RNA and the assembly of ribosome  subunits (ref reviews). Mammalian nucleoli disassemble during M-phase and reassemble during telophase around the tandemly repeated ribosomal  RNA gene clusters, which in human cells are located at the telomeres of the acrocentric chromosomes 13, 14, 15, 21 and 22 (Ref Hernandez  Verdun, maybe also Anthony JCB). Nucleoli are also surrounded by highly condensed, late-replicating heterochromatin whose composition has not  previously been well characterised. Here we show using a combination of fluorescence photoactivation and comparative fluorescence in situ  hybridisation (FISH) that nucleoli associate with specific loci contributed from most human chromosomes and not only from acrocentric  chromosomes. Chromosome regions associated with nucleoli in one cell cycle were observed also to associate with nucleoli in daughter nuclei.  Comparative high throughput sequencing of nucleolar-associated and total genomic DNA isolated from fractionated human HT1080 cells has mapped  loci on each chromosome that are preferentially associated with nucleoli. The identified loci show a high density of AT-rich sequence  elements and have low gene density and a striking enrichment in transcriptionally repressed genes. The data suggest that nucleolar  association of specific chromosome regions may play a role in chromosome orientation and positioning within the nucleus and in a higher level  regulation of gene expression patterns.