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Rôle de la nucléoline et de macroH2A dans la structure et la fonction du nucléole

Abstract : Ribosome synthesis starts in the nucleolus. The nucleolus structure is strongly influenced by ribosomal genes transcription. Ribosomal gene regulation is crucial for ribosome synthesis. The aim of this work was to define and open new methodological ways to characterize the role of macroH2A and nucleolin in the regulation of ribosomal genes expression. To date, MacroH2A is the only histone variant present in the nucleolus. Nucleolin is one of the major proteins of the nucleolus. The first part of this study is focused on the common carp, an original biological system, that adapts to temperature condition (winter and summer) by adjusting is gene expression. The results show that repression of ribosomal RNA expression, associated with a decrease of cellular activity, is concomitant with (i) nucleolar rearrangements, (ii) increase of macroH2A and nucleolin concentration and (iii) increase of DNA CpG methylation. Ribosomal genes expression appears to be linked to the level of macroH2A. To analyse the distribution of macroH2A on chromatin, we developed experiments based on extended chromatin fibers. We show that macroH2A colocalize with trimethylation of lysine 9 of H3, that is a marker of heterochromatin. Moreover, distribution of macroH2A is periodic, suggesting a role of this histone variant in a special chromatin organization. Finally, in the laboratory, we developed a cellular system based on nucleolin inhibition by RNA interference in HeLa cells. Two main results have emerged from the knockdown of nucleolin: decrease of pre-ribosomal RNA synthesis associated with nucleolar structure disruption and cell cycle arrest in mitosis leading to apoptosis. Thus, nucleolin is strongly implicated in the regulation of ribosomal genes expression.
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https://tel.archives-ouvertes.fr/tel-00145137
Contributor : Corinne Ivaldi <>
Submitted on : Tuesday, May 8, 2007 - 12:57:25 PM
Last modification on : Thursday, November 21, 2019 - 2:21:12 AM
Long-term archiving on: : Tuesday, April 6, 2010 - 11:41:37 PM

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  • HAL Id : tel-00145137, version 1

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Corinne Ivaldi. Rôle de la nucléoline et de macroH2A dans la structure et la fonction du nucléole. Biochimie [q-bio.BM]. Ecole normale supérieure de lyon - ENS LYON, 2007. Français. ⟨tel-00145137⟩

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