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Vertebrate embryos achieve developmental competency during zygotic genome activation (ZGA) by establishing chromatin states that silence yet poise developmental genes for subsequent lineage-specific activation. Here, we reveal the order of chromatin states in establishing developmental gene poising in preZGA zebrafish embryos. Poising is established at promoters and enhancers that initially contain open/permissive chromatin with ‘Placeholder’ nucleosomes (bearing H2A.Z, H3K4me1, and H3K27ac), and DNA hypomethylation. Silencing is initiated by the recruitment of polycomb repressive complex 1 (PRC1), and H2Aub1 deposition by catalytic Rnf2 during preZGA and ZGA stages. During postZGA, H2Aub1 enables Aebp2-containing PRC2 recruitment and H3K27me3 deposition. Notably, preventing H2Aub1 (via Rnf2 inhibition) eliminates recruitment of Aebp2-PRC2 and H3K27me3, and elicits transcriptional upregulation of certain developmental genes during ZGA. However, upregulation is independent of H3K27me3 – establishing H2Aub1 as the critical silencing modification at ZGA. Taken together, we reveal the logic and mechanism for establishing poised/silent developmental genes in early vertebrate embryos.

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