Recruitment to the nuclear periphery can alter expression of genes in human cells
The spatial organisation of the genome in the nucleus has a role in the regulation of gene expression. In vertebrates, chromosomal regions with low gene-density are located close to the nuclear periphery. Correlations have also been made between the transcriptional state of some genes and their loca...
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| Veröffentlicht in: | PLoS genetics 2008-03, Vol.4 (3), p.e1000039-e1000039 |
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| creator | Finlan, Lee E Sproul, Duncan Thomson, Inga Boyle, Shelagh Kerr, Elizabeth Perry, Paul Ylstra, Bauke Chubb, Jonathan R Bickmore, Wendy A |
| description | The spatial organisation of the genome in the nucleus has a role in the regulation of gene expression. In vertebrates, chromosomal regions with low gene-density are located close to the nuclear periphery. Correlations have also been made between the transcriptional state of some genes and their location near the nuclear periphery. However, a crucial issue is whether this level of nuclear organisation directly affects gene function, rather than merely reflecting it. To directly investigate whether proximity to the nuclear periphery can influence gene expression in mammalian cells, here we relocate specific human chromosomes to the nuclear periphery by tethering them to a protein of the inner nuclear membrane. We show that this can reversibly suppress the expression of some endogenous human genes located near the tethering sites, and even genes further away. However, the expression of many other genes is not detectably reduced and we show that location at the nuclear periphery is not incompatible with active transcription. The dampening of gene expression around the nuclear periphery is dependent on the activity of histone deacetylases. Our data show that the radial position within the nucleus can influence the expression of some, but not all, genes. This is compatible with the suggestion that re-localisation of genes relative to the peripheral zone of the nucleus could be used by metazoans to modulate the expression of selected genes during development and differentiation. |
| doi_str_mv | 10.1371/journal.pgen.1000039 |
| format | Article |
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In vertebrates, chromosomal regions with low gene-density are located close to the nuclear periphery. Correlations have also been made between the transcriptional state of some genes and their location near the nuclear periphery. However, a crucial issue is whether this level of nuclear organisation directly affects gene function, rather than merely reflecting it. To directly investigate whether proximity to the nuclear periphery can influence gene expression in mammalian cells, here we relocate specific human chromosomes to the nuclear periphery by tethering them to a protein of the inner nuclear membrane. We show that this can reversibly suppress the expression of some endogenous human genes located near the tethering sites, and even genes further away. However, the expression of many other genes is not detectably reduced and we show that location at the nuclear periphery is not incompatible with active transcription. The dampening of gene expression around the nuclear periphery is dependent on the activity of histone deacetylases. Our data show that the radial position within the nucleus can influence the expression of some, but not all, genes. 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This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: Finlan LE, Sproul D, Thomson I, Boyle S, Kerr E, et al. (2008) Recruitment to the Nuclear Periphery Can Alter Expression of Genes in Human Cells. 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In vertebrates, chromosomal regions with low gene-density are located close to the nuclear periphery. Correlations have also been made between the transcriptional state of some genes and their location near the nuclear periphery. However, a crucial issue is whether this level of nuclear organisation directly affects gene function, rather than merely reflecting it. To directly investigate whether proximity to the nuclear periphery can influence gene expression in mammalian cells, here we relocate specific human chromosomes to the nuclear periphery by tethering them to a protein of the inner nuclear membrane. We show that this can reversibly suppress the expression of some endogenous human genes located near the tethering sites, and even genes further away. However, the expression of many other genes is not detectably reduced and we show that location at the nuclear periphery is not incompatible with active transcription. The dampening of gene expression around the nuclear periphery is dependent on the activity of histone deacetylases. Our data show that the radial position within the nucleus can influence the expression of some, but not all, genes. 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In vertebrates, chromosomal regions with low gene-density are located close to the nuclear periphery. Correlations have also been made between the transcriptional state of some genes and their location near the nuclear periphery. However, a crucial issue is whether this level of nuclear organisation directly affects gene function, rather than merely reflecting it. To directly investigate whether proximity to the nuclear periphery can influence gene expression in mammalian cells, here we relocate specific human chromosomes to the nuclear periphery by tethering them to a protein of the inner nuclear membrane. We show that this can reversibly suppress the expression of some endogenous human genes located near the tethering sites, and even genes further away. However, the expression of many other genes is not detectably reduced and we show that location at the nuclear periphery is not incompatible with active transcription. The dampening of gene expression around the nuclear periphery is dependent on the activity of histone deacetylases. Our data show that the radial position within the nucleus can influence the expression of some, but not all, genes. This is compatible with the suggestion that re-localisation of genes relative to the peripheral zone of the nucleus could be used by metazoans to modulate the expression of selected genes during development and differentiation.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>18369458</pmid><doi>10.1371/journal.pgen.1000039</doi><oa>free_for_read</oa></addata></record> |
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| subjects | Base Sequence Binding Sites - genetics Cell Biology/Gene Expression Cell Biology/Nuclear Structure and Function Cell Line Cell Nucleus - genetics Cell Nucleus - metabolism Chromosomes Chromosomes, Human - genetics Cloning Colleges & universities DNA Primers - genetics DNA-Binding Proteins - genetics DNA-Binding Proteins - metabolism Gene Expression Genetics Genetics and Genomics/Epigenetics Genetics and Genomics/Gene Expression Genetics and Genomics/Nuclear Structure and Function Genomes Histone Deacetylases - metabolism Humans In Situ Hybridization, Fluorescence Lac Operon Membrane Proteins - genetics Membrane Proteins - metabolism Metazoa Nuclear Envelope - genetics Nuclear Envelope - metabolism Oligonucleotide Array Sequence Analysis Polymerase Chain Reaction Proteins Recombinant Fusion Proteins - genetics Recombinant Fusion Proteins - metabolism Saccharomyces cerevisiae Suppression, Genetic |
| title | Recruitment to the nuclear periphery can alter expression of genes in human cells |
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