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Specific nuclear envelope transmembrane proteins can promote the location of chromosomes to and from the nuclear periphery

Nikolaj Zuleger1, Shelagh Boyle2, David A Kelly1, Jose I de las Heras1, Vassiliki Lazou1, Nadia Korfali1, Dzmitry G Batrakou1, K Natalie Randles34, Glenn E Morris34, David J Harrison5, Wendy A Bickmore2 and Eric C Schirmer1*

Author affiliations

1 The Wellcome Trust Centre for Cell Biology, University of Edinburgh, Mayfield Road, Edinburgh, EH9 3JR, UK

2 MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, Crewe Road, Edinburgh, EH4 2XU, UK

3 Wolfson Centre for Inherited Neuromuscular Disease, RJAH Orthopaedic Hospital, Twympath Lane, Oswestry, SY10 7AG, UK

4 Institute for Science and Technology in Medicine, Keele University, Keele, Staffordshire, ST4 7QB, UK

5 School of Medicine, Medical andBiological Sciences, University of St Andrews, North Haugh, St Andrews, KY16 9TF, UK

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Citation and License

Genome Biology 2013, 14:R14  doi:10.1186/gb-2013-14-2-r14

Published: 15 February 2013

Abstract

Background

Different cell types have distinctive patterns of chromosome positioning in the nucleus. Although ectopic affinity-tethering of specific loci can be used to relocate chromosomes to the nuclear periphery, endogenous nuclear envelope proteins that control such a mechanism in mammalian cells have yet to be widely identified.

Results

To search for such proteins, 23 nuclear envelope transmembrane proteins were screened for their ability to promote peripheral localization of human chromosomes in HT1080 fibroblasts. Five of these proteins had strong effects on chromosome 5, but individual proteins affected different subsets of chromosomes. The repositioning effects were reversible and the proteins with effects all exhibited highly tissue-restricted patterns of expression. Depletion of two nuclear envelope transmembrane proteins that were preferentially expressed in liver each reduced the normal peripheral positioning of chromosome 5 in liver cells.

Conclusions

The discovery of nuclear envelope transmembrane proteins that can modulate chromosome position and have restricted patterns of expression may enable dissection of the functional relevance of tissue-specific patterns of radial chromosome positioning.