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Published online
doi:10.1083/jcb.200607054
The Journal of Cell Biology, Vol. 176, No. 5, 593-603
The Rockefeller University Press, 0021-9525 $30.00
© Malhas et al.
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Article

Defects in lamin B1 expression or processing affect interphase chromosome position and gene expression



Ashraf Malhas1, Chiu Fan Lee2, Rebecca Sanders3, Nigel J. Saunders1, and David J. Vaux1

1 Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, England, UK
2 Department of Physics, Clarendon Laboratory, University of Oxford, Oxford OX1 3PU, England, UK
3 Department of Biochemistry, University of Oxford, Oxford OX1 3QU2, England, UK

Correspondence to David J. Vaux: david.vaux{at}path.ox.ac.uk

Radial organization of nuclei with peripheral gene-poor chromosomes and central gene-rich chromosomes is common and could depend on the nuclear boundary as a scaffold or position marker. To test this, we studied the role of the ubiquitous nuclear envelope (NE) component lamin B1 in NE stability, chromosome territory position, and gene expression. The stability of the lamin B1 lamina is dependent on lamin endoproteolysis (by Rce1) but not carboxymethylation (by Icmt), whereas lamin C lamina stability is not affected by the loss of full-length lamin B1 or its processing. Comparison of wild-type murine fibroblasts with fibroblasts lacking full-length lamin B1, or defective in CAAX processing, identified genes that depend on a stable processed lamin B1 lamina for normal expression. We also demonstrate that the position of mouse chromosome 18 but not 19 is dependent on such a stable nuclear lamina. The results implicate processed lamin B1 in the control of gene expression as well as chromosome position.

R. Sanders's current address is Department of Clinical Biochemistry, University of Cambridge, Cambridge CB2 2QR, England, UK.

Abbreviations used in this paper: FLIP, fluorescence loss in photobleaching; FTI, farnesyl transferase inhibitor; Mbp, Mega bp; MIAME, minimum information for annotation of microarray experiments; NE, nuclear envelope; NPC, nuclear pore complex; qRT-PCR, quantitative real-time PCR; ROI, region of interest; WT, wild-type.


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