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The EAST protein of Drosophila controls an expandable nuclear endoskeleton

Abstract

The high degree of structural order inside the nucleus suggests the existence of an internal nucleoskeleton. Our studies on the east gene of Drosophila, using the larval salivary gland polytene nucleus as a model, demonstrate the involvement of an extrachromosomal nuclear structure in modulating nuclear architecture. EAST, a novel ubiquitous protein, the product of the east (enhanced adult sensory threshold) locus, is localized to an extrachromosomal domain of the nucleus. Nuclear levels of EAST are increased in response to heat shock. Increase in nuclear EAST, whether caused by heat shock or by transgenic overexpression, results in the expansion of the extrachromosomal domain labelled by EAST, with a concomitant increase in the spacing between chromosomes. Moreover, EAST functions to promote the preferential accumulation of the proteins CP60 and actin in extrachromosomal regions of the nucleus. We propose that EAST mediates the assembly of an expandable nuclear endoskeleton which, through alterations of its volume, can modulate the spatial arrangement of chromosomes.

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Figure 1: Genomic organization of east and the sequence of the EAST protein.
Figure 2: Nuclear and extrachromosomal localization of EAST.
Figure 3: EAST is a component of an expandable nuclear domain that also contains CP60.
Figure 4: Overexpression of EAST leads to an expansion of the END.
Figure 5: Correlation of EAST protein and nuclear volume.
Figure 6: EAST modulates the levels of nuclear actin.
Figure 7: Overexpression of EAST in diploid cells can expand extrachromosomal structures.
Figure 8: Proposed mechanism for the involvement of EAST in shaping nuclear architecture.

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Acknowledgements

We thank V. Rodrigues for discussion and comments on the manuscript, J. Kaur and V. Rodrigues for the east fly stocks prior to publication, G. Udolph for help with the germline transformation, A. Brand for the tau-GFP stock, J. Gruenbaum for anti-lamin, J. Raff for anti-CP60, R. Saint for the His2AvDGFP line and the Bloomington Stock Center for stocks. We thank the Institute of Molecular and Cell Biology for financial support.

Correspondence and requests for materials should be addressed to W.C. The Drosophila east cDNA sequence has been deposited in GenBank, accession number AF242291.

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Wasser, M., Chia, W. The EAST protein of Drosophila controls an expandable nuclear endoskeleton. Nat Cell Biol 2, 268–275 (2000). https://doi.org/10.1038/35010535

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