June, 8th 2005
Gene expression is governed by spatial organization in the nucleus
Teams at the Institut Pasteur, in collaboration with the CNRS *, have recently discovered an fundamental aspect of cell biology and gene regulation. The results of this work, published in Nature, were obtained by means of the most up-to-date microscopy and image analysis technologies. The researchers were able to observe the position of a gene in real time during its activation and to found that it is confined to the edges of the nucleus. This work opens up the way to understanding how disorganization of nuclear structures may have a role in the occurrence of a number of genetic diseases and cancers.
Researchers at the Institut Pasteur and CNRS, in collaboration with teams at Heidelberg University (Germany) and Paris VI University, have made marked progress in detecting regulation linked to the spatial organization of genes near the nuclear envelope. By studying a gene of the yeast S. cerevisae as a model, they have demonstrated that when activated, the mobility of this gene is reduced and confined to the edge of the nucleus where metabolic regulation of gene expression and the transfer of its genetic message take place. To do this, they used the latest technology combining very high resolution dynamic microscopy, sophisticated image analysis software and powerful computer processing.
In addition, the researchers have identified the molecular players that mediate the change in the spatial positioning of activates genes, factors which have mainly been known for their role in gene activation. It is therefore clearly apparent that gene regulation is closely related to the gene’s position within the nuclear space. This confers a regulating role on spatial organization in the nucleus.
Combined with the results published by a research group at Basel University, this work shows that gene regulation is not solely dependent on specific DNA sequences and the coordinated action of factors which bind to them. It has now been established that genetic information is coded and decoded as a function of the three-dimensional positioning and environment of the gene. Thus it would seem that in the course of evolution, cells became capable of using three dimensions in the cellular and nuclear space as a means of coding biological information. The nuclear space and its architectural organization therefore represent the required level of integrated information for the transmission and modification of hereditary and functional information.
In light of this work, it is vital to re-examine nuclear organization from a new angle. The use of information coded by the spatial and architectural organization of the nucleus might explain why the intactness of the cell envelope is compromised in several hereditary diseases, such as dystrophia. Similarly, we may find the key to understanding why there is frequently considerable deformation in the morphology and integrity of the nucleus in cancer cells. The results obtained suggest that these deformations could be the cause rather than the consequence of cancerous changes in the cell.
Ghislain G. Cabal (1), Auguste Genovesio (2), Susana Rodriguez-Navarro (4), Christophe Zimmer (2), Olivier Gadal (1), Annick Lesne (5), Henri Buc (3), Frank Feuerbach-Fournier (1), Jean-Christophe Olivo-Marin (2), Eduard C. Hurt (4) & Ulf Nehrbass (1)
1. Unité de Biologie Cellulaire du Noyau, Institut Pasteur
2. Unité d’Analyse d’Images Quantitative, Institut Pasteur-CNRS
3. Département de Biologie Cellulaire et Infection, Institut Pasteur
4. Biochemie-Zentrum der Universität Heidelberg, Allemagne
5. Laboratoire de Physique Théorique de la Matière Condensée, Université Pierre et Marie Curie, Paris VI
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