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Phosphorylation of histone H3 threonine 118 (H3 T118ph) weakens histone DNA-contacts, disrupting the nucleosome structure. We show that Aurora-A mediated H3 T118ph occurs at pericentromeres and chromosome arms during prophase and is lost upon chromosome alignment. Expression of H3 T118E or H3 T118I (a SIN mutation that bypasses the need for the ATP-dependent nucleosome remodeler SWI/SNF) leads to mitotic problems including defects in spindle attachment, delayed cytokinesis, reduced chromatin packaging, cohesion loss, cohesin and condensin I loss in human cells. In agreement, overexpression of Aurora-A leads to increased H3 T118ph levels, causing cohesion loss, and reduced levels of cohesin and condensin I on chromatin. Normal levels of H3 T118ph are important because it is required for development in fruit flies. We propose that H3 T118ph alters the chromatin structure during specific phases of mitosis to promote timely condensin I and cohesin disassociation, which is essential for effective chromosome segregation. DOI: http://dx.doi.org/10.7554/eLife.11402.001, eLife digest In every one of our cells, our DNA is wrapped together with histone proteins to make a structure called chromatin. When a cell divides, each newly formed daughter cell must receive an identical set of chromatin. As part of this process, the chromatin is copied and then compacted, which causes a characteristic “X”-shaped chromosome to form. This “X” shape is actually made up of two identical parts, or chromatids, that are joined together until a specific time during cell division. If chromosomes separate too early or too late, the DNA will not distribute evenly to daughter cells, which could lead to diseases including cancer. Histone modifications are small chemical changes on the histone proteins that the DNA wraps around. Previous research identified a new histone modification that is located at an important contact point between the DNA and a particular histone protein. However, the role of this modification in living cells was not clear. Wike et al. have now determined that in animal cells, this histone modification occurs immediately before the chromatids separate and at specific locations along the chromosomes. The amount of this histone modification is very important: in cells with too much of the modification, the chromosomes compacted incorrectly and the chromatids separated too soon. As a result, the chromosomes were incorrectly distributed among the daughter cells. Wike et al. also show that an enzyme called Aurora-A kinase is responsible for making this histone modification. The next challenge will be to understand how the Aurora-A kinase knows when and where to add the histone modification to the chromosome. This will help us to understand how the overproduction of Aurora-A causes cancer. DOI: http://dx.doi.org/10.7554/eLife.11402.002

International audience; Confinement of enzymatic reactions to nuclear and chromosomal subdomains regulates functional organization of the nucleus. Aurora-B kinase regulates cell cycle dependent phosphorylation of chromosomal substrates through sequential localization to a series of sites on chromosomes and the mitotic spindle. In G2 nuclei, Aurora-B recruitment to heterochromatin restricts histone H3S10 phosphorylation to a domain around centromeres (pericentromeres). However, no intrinsic chromosomal determinants have been implicated in Aurora-B recruitment to interphase pericentromeres. Using cyclin B1 as a cell cycle marker, we found that the great majority of nuclei exhibiting H3S10 phosphorylated foci were positive for cyclin B1, thus revealing that H3S10 phosphorylation arises at pericentromeres during late S phase and persists in G2. By immuno-fluorescent in situ hybridization, Aurora-B and H3S10 phosphorylated foci were found more frequently at larger pericentromeres than at smaller ones, revealing a preferential phosphorylation of pericentromeres, exhibiting a high density of methyl cytosines. Disruption of DNA methylation inhibited pericentromeric Aurora-B targeting and H3S10 phosphorylation in G2 nuclei, thus demonstrating the role of DNA methylation in Aurora-B targeting to pericentromeres. These results favour the idea that DNA methylation maintains a local environment essential for regulating the functional properties of sub-chromosomal domains during S-G2 progression.

Dynamic histone acetylation, catalyzed by lysine acetyltransferases and HDACs, is critical to IEG expression. Expression of IEGs, such as FOSL1, is induced by several signal transduction pathways resulting in activation of the protein kinase MSK and phosphorylation of histone H3 at serine 10 of nucleosomes (the nucleosome response) at the upstream promoter and regulatory region of target genes. HDAC inhibitors prevent FOSL1 gene induction and the association of HDAC1, 2 and 3 with the gene body. However, HDAC inhibitors did not prevent the nucleosome response. Thus HDAC inhibitors perturb events downstream of the nucleosome response required for FOSL1 transcription initiation.