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First published online 30 May 2006
doi: 10.1242/jcs.02965

Journal of Cell Science 119, 2518-2531 (2006)
Published by The Company of Biologists 2006
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Research Article

PML nuclear bodies are highly organised DNA-protein structures with a function in heterochromatin remodelling at the G2 phase

J. J. Luciani1, D. Depetris1, Y. Usson2, C. Metzler-Guillemain1, C. Mignon-Ravix1, M. J. Mitchell1, A. Megarbane3, P. Sarda4, H. Sirma5, A. Moncla6, J. Feunteun7 and M.-G. Mattei1,*

1 Inserm, Université de la Méditerranée, UMR491, Faculté de Médecine, 27 Boulevard Jean Moulin, 13385 Marseille, France
2 TIMC UMR5525 CNRS, Faculté de Médecine, 38706 La Tronche, France
3 Département de Génétique Médicale, Université Saint Joseph, 5076 Beirut, Lebanon
4 Service de Génétique Médicale, Hôpital Arnaud de Villeneuve, 34059 Montpellier, France
5 Heinrich Pette Institute for Experimental Virology and Immunology, 20206 Hamburg, Germany
6 Département de Génétique Médicale, Hôpital d'enfants de la Timone, 13385 Marseille, France
7 Laboratoire de Génétique Oncologique, Institut Gustave Roussy, 94805 Villejuif, France

* Author for correspondence (e-mail: genevieve.mattei{at}medecine.univ-mrs.fr)

Accepted 1 March 2006

We have recently demonstrated that heterochromatin HP1 proteins are aberrantly distributed in lymphocytes of patients with immunodeficiency, centromeric instability and facial dysmorphy (ICF) syndrome. The three HP1 proteins accumulate in one giant body over the 1qh and 16qh juxtacentromeric heterochromatins, which are hypomethylated in ICF. The presence of PML (promyelocytic leukaemia) protein within this body suggests it to be a giant PML nuclear body (PML-NB). The structural integrity of PML-NBs is of major importance for normal cell functioning. Nevertheless, the structural organisation and the functions of these nuclear bodies remain unclear. Here, we take advantage of the large size of the giant body to demonstrate that it contains a core of satellite DNA with proteins being organised in ordered concentric layers forming a sphere around it. We extend these results to normal PML-NBs and propose a model for the general organisation of these structures at the G2 phase. Moreover, based on the presence of satellite DNA and the proteins HP1, BRCA1, ATRX and DAXX within the PML-NBs, we propose that these structures have a specific function: the re-establishment of the condensed heterochromatic state on late-replicated satellite DNA. Our findings that chromatin-remodelling proteins fail to accumulate around satellite DNA in PML-deficient NB4 cells support a central role for PML protein in this cellular function.

Key words: PML nuclear body, Heterochromatin, Chromatin-remodelling function, G2 phase, ICF syndrome, XY body




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