Histone variants H2BFWT and macroH2A1: from structure to epigentic function ; Variants d'histones H2BFWT et macroH2A1: de la structure à la fonction épigénétique

In addition to conventional histones, non-allelic variants are also expressed in low amount in eukaryotic cells. Recent data have revealed that histone variants assume roles in various processes within the cell including DNA repair, chromosome segregation and transcriptional control. The aim of my study was to highlight some biological functions harbored by histone variants. My investigations focused on two variants: the uncharacterized H2BFWT, which plays a role in human spermatogenesis and macroH2A1, which has an unclear function in transcriptional silencing. We show that, despite its huge divergence with H2B, the presence of H2BFWT does not affect the overall structure of the nucleosome. Importantly, in contrast to somatic H2B, H2BFWT was unable to recruit chromosome condensation factors and to participate in the assembly of mitotic chromosomes. This difference towards chromosome assembly suggests that H2BFWT might be involved in chromatin architecture. In order to bring new insights about macroH2A1 function in vivo we have disrupted macroH2A1 expression in mice by gene targeting. Many studies have been addressed macroH2A1 function, however its biological role remains unclear. MacroH2A1 is three times bigger than H2A and carries a C-terminal extension of unknown function. Initially macroH2A1 had been reported to be predominantly located on the inactive X chromosome in female. The biological significance of this enrichment is totally unknown. In vitro, the presence of macroH2A1 interferes with transcription. Recent studies show that methylated DNA sequences including imprinted genes and retrotransposons are enriched in macroH2A1. It has been reported that macroH2A recruitment on retrotransposons is mediated by DNA methylation, which is absolutely required for their silencing. We hypothesized that methylation of CpG dinucleotides in retrotransposons might achieve transcriptional repression through recruitment of macroH2A1. The study of the mice phenotype shows that contrary to the current view, macroH2A1 is not ...