Mitosis epigenetic regulation – functional analysis of the centromere "histone code"
The code histone hypothesis, formulated early in the 21th century, postulates that distinct histone modifications, on one or more histone tails, act sequentially or in combination to form a code that is read by other proteins to bring about distinct downstream events. Although it has been extensively studied to explain transcription regulation mechanisms, the histone code is involved in virtually all chromatin-related functions (replication, DNA repair, homologous recombination, etc.)
Our project aims at decyphering this code within the centromeric nucleosomes and at understanding the role of centromeric histone modifications in mitotic functions such as establishment and maintenance of the kinetochore attachment checkpoint, sister chromatid cohesion or kinetochore formation. In particular, we have characterized the function of a specific histone deacetylase isoform, HDAC3, in the deacetylation of a centromeric histone and its role in sister chromatid cohesion.
Given that mitosis is a favorite anticancer “shooting window”, we are also interested in the enzymes that catalyze histone modifications involved in mitotic progression. Some of them may indeed become good therapeutic targets.