Heidi G.E. Sutherland, Gail K. Mumford, Kathryn Newton, Lisa V. Ford, Rachel Farrall, Graham Dellaire, Javier F. Cáceres and Wendy A. Bickmore@
MRC Human Genetics Unit, Crewe Road, Edinburgh EH4 2XU, UK
@To whom correspondence should be addressed. Tel: +44
131 332 2472; Fax: +44 131 343 2620;
Email: w.bickmore@hgu.mrc.ac.uk
Many nuclear components participating in related pathways appear
concentrated in specific areas of the mammalian nucleus. The importance
of this organization is attested to by the dysfunction that correlates
with mis-localization of nuclear proteins in human disease and cancer.
Determining the sub-nuclear localization of proteins is therefore important
for understanding genome regulation and function, and it also provides
clues to function for novel proteins. However, the complexity of proteins
in the mammalian nucleus is too large to tackle this on a protein by protein
basis. Large-scale approaches to determining protein function and sub-cellular
localization are required. We have used a visual gene trap screen to identify
more than 100 proteins, many of which are normal, located within compartments
of the mouse nucleus. The most common discrete localizations detected are
at the nucleolus and the splicing speckles
and on chromosomes. Proteins at the nuclear periphery, or in other
nuclear foci, have also been identified. Several of the proteins have been
implicated in human disease or cancer, e.g. ATRX, HMGI-C, NBS1 and EWS,
and the gene-trapped proteins provide a route into further understanding
their function. We find that sequence motifs are often shared amongst proteins
co-localized within the same sub-nuclear compartment. Conversely, some
generally abundant motifs are lacking from the proteins concentrated in
specific areas of the nucleus. This suggests that we may be able to predict
sub-nuclear localization for proteins in databases based on their sequence.
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