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Subnuclear localisation is associated with gene expression more than parental origin at the imprinted Dlk1-Dio3 locus.

Published version
Peer-reviewed

Type

Article

Change log

Authors

Hülsmann, Lisa C 
Edwards, Carol 

Abstract

At interphase, de-condensed chromosomes have a non-random three-dimensional architecture within the nucleus, however, little is known about the extent to which nuclear organisation might influence expression or vice versa. Here, using imprinting as a model, we use 3D RNA- and DNA-fluorescence-in-situ-hybridisation in normal and mutant mouse embryonic stem cell lines to assess the relationship between imprinting control, gene expression and allelic distance from the nuclear periphery. We compared the two parentally inherited imprinted domains at the Dlk1-Dio3 domain and find a small but reproducible trend for the maternally inherited domain to be further away from the periphery however we did not observe an enrichment of inactive alleles in the immediate vicinity of the nuclear envelope. Using Zfp57KO ES cells, which harbour a paternal to maternal epigenotype switch, we observe that expressed alleles are significantly further away from the nuclear periphery. However, within individual nuclei, alleles closer to the periphery are equally likely to be expressed as those further away. In other words, absolute position does not predict expression. Taken together, this suggests that whilst stochastic activation can cause subtle shifts in localisation for this locus, there is no dramatic relocation of alleles upon gene activation. Our results suggest that transcriptional activity, rather than the parent-of-origin, defines subnuclear localisation at an endogenous imprinted domain.

Description

Keywords

Alleles, Animals, Calcium-Binding Proteins, Cell Nucleus, Embryonic Stem Cells, Gene Expression, Genomic Imprinting, Iodide Peroxidase, Membrane Proteins, Mice, Parents

Journal Title

PLoS Genet

Conference Name

Journal ISSN

1553-7390
1553-7404

Volume Title

18

Publisher

Public Library of Science (PLoS)
Sponsorship
Medical Research Council (MR/J001597/1)
Wellcome Trust (095606/Z/11/Z)