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Organisation de la chromatine et son lien avec la réplication de l'ADN

Abstract : Chromatin organization is of functional significance to control the gene expression program. However, its interplay with DNA replication program is less known. Though the capture of chromosomal interactions and cell imaging, we studied the links between the high-order folding of chromatin and the replication timing. This analysis, which has been performed in human lymphoblastoid cells, in peripheral blood mononuclear cells (PBMC), and in a myeloid leukemia cell line with erythroid properties, allowed the identification of structural domains in the nucleus. These domains are quite isolated from each other and their boundaries coincide with early-initiation zones. In addition, our study shows that these early-initiation zones preferentially interact with each other. These interactions have been observed between neighboring early-initiation zones (genomic separation around 1 to few megabases) but also along the whole chromosome. The late-replicated loci interact with their counterparts as well, leading to a nuclear segregation of the loci according to their replication timing. These results are sustained by distance measurements in in-situ hybridizations which show that loci replicated at the beginning of S-phase are closer than expected. Our work also reveals that chromatin organization is similar in cells blocked in G0 phase (quiescent PBMC), demonstrating that it does not result from the cells in S-phase. Taken together, these results provide direct clues for a robust chromatin organization, common to cycling and resting cells, and related to the replication timing at different scales.
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https://theses.hal.science/tel-00733254
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Submitted on : Tuesday, September 18, 2012 - 11:57:20 AM
Last modification on : Wednesday, November 20, 2019 - 7:26:52 AM
Long-term archiving on: : Wednesday, December 19, 2012 - 3:44:31 AM

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  • HAL Id : tel-00733254, version 1

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Benoît Moindrot. Organisation de la chromatine et son lien avec la réplication de l'ADN. Biologie cellulaire. Ecole normale supérieure de lyon - ENS LYON, 2012. Français. ⟨NNT : 2012ENSL0728⟩. ⟨tel-00733254⟩

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