The shared genomic architecture of human nucleolar organizer regions
- Ioanna Floutsakou1,4,
- Saumya Agrawal2,4,
- Thong T. Nguyen3,4,
- Cathal Seoighe3,
- Austen R.D. Ganley2 and
- Brian McStay1,5
- 1Centre for Chromosome Biology, School of Natural Sciences, National University of Ireland, Galway, Galway, Ireland;
- 2Institute of Natural and Mathematical Sciences, Massey University, Auckland 0632, New Zealand;
- 3School of Mathematics, Statistics and Applied Mathematics, National University of Ireland, Galway, Galway, Ireland
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↵4 These authors contributed equally to this work.
Abstract
The short arms of the five acrocentric human chromosomes harbor sequences that direct the assembly and function of the nucleolus, one of the key functional domains of the nucleus, yet they are absent from the current human genome assembly. Here we describe the genomic architecture of these human nucleolar organizers. Sequences distal and proximal to ribosomal gene arrays are conserved among the acrocentric chromosomes, suggesting they are sites of frequent recombination. Although previously believed to be heterochromatic, characterization of these two flanking regions reveals that they share a complex genomic architecture similar to other euchromatic regions of the genome, but they have distinct genomic characteristics. Proximal sequences are almost entirely segmentally duplicated, similar to the regions bordering centromeres. In contrast, the distal sequence is predominantly unique to the acrocentric short arms and is dominated by a very large inverted repeat. We show that the distal element is localized to the periphery of the nucleolus, where it appears to anchor the ribosomal gene repeats. This, combined with its complex chromatin structure and transcriptional activity, suggests that this region is involved in nucleolar organization. Our results provide a platform for investigating the role of NORs in nucleolar formation and function, and open the door for determining the role of these regions in the well-known empirical association of nucleoli with pathology.
Footnotes
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↵5 Corresponding author
E-mail brian.mcstay{at}nuigalway.ie
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[Supplemental material is available for this article.]
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Article published online before print. Article, supplemental material, and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.157941.113.
Freely available online through the Genome Research Open Access option.
- Received March 21, 2013.
- Accepted August 28, 2013.
This article, published in Genome Research, is available under a Creative Commons License (Attribution-NonCommercial 3.0 Unported), as described at http://creativecommons.org/licenses/by-nc/3.0/.
