title: Recruitment to the nuclear periphery can alter expression of genes in human cells.
abstract: 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.
authors: MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom.
authors: Lee E
authors: LE
authors: Finlan
authors: Duncan
authors: D
authors: Sproul
authors: Inga
authors: I
authors: Thomson
authors: Shelagh
authors: S
authors: Boyle
authors: Elizabeth
authors: E
authors: Kerr
authors: Paul
authors: P
authors: Perry
authors: Bauke
authors: B
authors: Ylstra
authors: Jonathan R
authors: JR
authors: Chubb
authors: Wendy A
authors: WA
authors: Bickmore
mesh_terms: D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D002460:Cell Line; D002467:Cell Nucleus / Q000235:genetics* / Q000378:metabolism; D002877:Chromosomes, Human / Q000235:genetics; D017931:DNA Primers / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007763:Lac Operon; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D009685:Nuclear Envelope / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D013489:Suppression, Genetic
chemical_list: D017931:DNA Primers; D004268:DNA-Binding Proteins; D008565:Membrane Proteins; D011993:Recombinant Fusion Proteins; C093413:lamina-associated polypeptide 2; D006655:Histone Deacetylases