Histone H4 post-translational modifications in chordate mitotic and endoreduplicative cell cycles.

Histone post-translational modifications mark distinct structural and functional chromatin states but little is known of their involvement in the progression of different cell cycle types across phylogeny. We compared temporal and spatial dynamics of histone H4 post-translational modifications during both mitotic and endoreduplicative cycles of the urochordate, Oikopleura dioica, and proliferating mammalian cells. Endocycling cells showed no signs of chromosome condensation or entry into mitosis. They exhibited an evolution of replication patterns indicative of reduced chromatin compartmentalization relative to proliferating mammalian cells. In the latter cells, published cell cycle profiles of histone H4 acetylated at lysine 16 (H4AcK16) or dimethylated at lysine 20 (H4Me2K20) are disputed. Our results, using different, widely used H4AcK16 antibodies, revealed significant antibody-specific discrepancies in spatial and temporal cell cycle regulation of this modification, with repercussions for interpretation of previous immunofluorescence and immunoprecipitation data based on these reagents. On the other hand, three different antibodies to H4Me2K20 revealed similar cell cycle profiles of this modification that were conserved throughout the mitotic cell cycle in urochordate and mammalian cells, with accumulation at mitosis and a decrease during S-phase. H4Me2K20 also cycled in endocycles, indicating that dynamics of this modification are not strictly constrained by the mitotic phase of the cell cycle and suggesting additional roles during G- and S-phase progression. This article contains Supplementary Material available at http://www.mrw.interscience.wiley.com/suppmat/0730-2312/suppmat/2005/95/spada.html.