The dynamic three-dimensional organization of the diploid yeast genome
Abstract
The budding yeast Saccharomyces cerevisiae is a long-standing model for the three-dimensional organization of eukaryotic genomes. However, even in this well-studied model, it is unclear how homolog pairing in diploids or environmental conditions influence overall genome organization. Here, we performed high-throughput chromosome conformation capture on diverged Saccharomyces hybrid diploids to obtain the first global view of chromosome conformation in diploid yeasts. After controlling for the Rabl-like orientation using a polymer model, we observe significant homolog proximity that increases in saturated culture conditions. Surprisingly, we observe a localized increase in homologous interactions between the HAS1-TDA1 alleles specifically under galactose induction and saturated growth. This pairing is accompanied by relocalization to the nuclear periphery and requires Nup2, suggesting a role for nuclear pore complexes. Together, these results reveal that the diploid yeast genome has a dynamic and complex 3D organization.
Data availability
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Data from The dynamic three-dimensional organization of the diploid yeast genomePublicly available at the NCBI Gene Expression Omnibus (accession no: GSE88952).
Article and author information
Author details
Funding
National Institutes of Health (GM080484 to JHB P41GM103533 to MJD U54 DK107979 to JS and WSN)
- William S Noble
- Jason H Brickner
- Jay Shendure
- Maitreya J Dunham
National Science Foundation (graduate research fellowship DGE-1256082 to SK 1516330 to MJD)
- Seungsoo Kim
Howard Hughes Medical Institute (JS is an investigator of HHMI MJD was supported in part by a Faculty Scholar grant from HHMI)
- Jay Shendure
- Maitreya J Dunham
Canadian Institute for Advanced Research (MJD is a senior fellow in the Genetic Networks Program)
- Maitreya J Dunham
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Bing Ren, University of California, San Diego School of Medicine, United States
Version history
- Received: November 24, 2016
- Accepted: May 22, 2017
- Accepted Manuscript published: May 24, 2017 (version 1)
- Version of Record published: June 19, 2017 (version 2)
Copyright
© 2017, Kim et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Histone H1 participates in chromatin condensation and regulates nuclear processes. Human somatic cells may contain up to seven histone H1 variants, although their functional heterogeneity is not fully understood. Here, we have profiled the differential nuclear distribution of the somatic H1 repertoire in human cells through imaging techniques including super-resolution microscopy. H1 variants exhibit characteristic distribution patterns in both interphase and mitosis. H1.2, H1.3, and H1.5 are universally enriched at the nuclear periphery in all cell lines analyzed and co-localize with compacted DNA. H1.0 shows a less pronounced peripheral localization, with apparent variability among different cell lines. On the other hand, H1.4 and H1X are distributed throughout the nucleus, being H1X universally enriched in high-GC regions and abundant in the nucleoli. Interestingly, H1.4 and H1.0 show a more peripheral distribution in cell lines lacking H1.3 and H1.5. The differential distribution patterns of H1 suggest specific functionalities in organizing lamina-associated domains or nucleolar activity, which is further supported by a distinct response of H1X or phosphorylated H1.4 to the inhibition of ribosomal DNA transcription. Moreover, H1 variants depletion affects chromatin structure in a variant-specific manner. Concretely, H1.2 knock-down, either alone or combined, triggers a global chromatin decompaction. Overall, imaging has allowed us to distinguish H1 variants distribution beyond the segregation in two groups denoted by previous ChIP-Seq determinations. Our results support H1 variants heterogeneity and suggest that variant-specific functionality can be shared between different cell types.