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Déchiffrer le code histone : épigénétique et toxicologie placentaire

Abstract : While acting upon chromatin compaction, histone post-translational modifications (PTMs) are involved in modulating gene expression through histone–DNA affinity and protein–protein interactions. These dynamic and environment-sensitive modifications are constitutive of the histone code that reflects the transient transcriptional state of the chromatin. Here we describe a global screening approach for revealing epigenetic disruption at the histone level. This original approach enables fast and reliable relative abundance comparison of histone PTMs and variants in human cells within a single LC-MS experiment. As a proof of concept, we exposed BeWo human choriocarcinoma cells to sodium butyrate (SB), a universal histone deacetylase (HDAC) inhibitor. Histone acide xtracts equally representing 3 distinct classes, Control, 1 mM and 2.5 mM SB, we reanalyzed using ultra-performance liquid chromatography coupled with a hybrid quadrupoletime-of-flight mass spectrometer (UPLC-QTOF-MS). Multivariate statistics allowed us to discriminate control from treated samples based on differences in the acetylation level of several histone forms. We then applied the same procedure to cells treated with 1 μMB[a]P and suceeded in revealing two markers of chromatin remodeling in relation withgenotoxic properties of B[a]P. Indeed, this untargeted histonomic approach could be auseful exploratory tool in many cases of environmental xenobiotic exposure when histone code disruption is suspected.
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https://tel.archives-ouvertes.fr/tel-01195983
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  • HAL Id : tel-01195983, version 1

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Raphaël Bilgraer. Déchiffrer le code histone : épigénétique et toxicologie placentaire. Toxicologie. Université René Descartes - Paris V, 2014. Français. ⟨NNT : 2014PA05P627⟩. ⟨tel-01195983⟩

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