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

JJ Luciani, D Depetris, Y Usson… - Journal of cell …, 2006 - journals.biologists.com
JJ Luciani, D Depetris, Y Usson, C Metzler-Guillemain, C Mignon-Ravix, MJ Mitchell…
Journal of cell science, 2006journals.biologists.com
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 …
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.
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