However, the phosphorylation status of LB3 before and during oocyte maturation remains unclear

osome condensation becomes evident at the onset of mitosis, H3 phosphorylation continues increasing from prophase to metaphase due to transactivation of Aurora B and a positive feedback loop involving Haspin.9 In addition, other kinases can be recruited to ensure robust H3 phosphorylation.10 Histone phosphorylation is so abundant that phosphorylation-dependent conformational changes were occasionally thought to drive chromatin condensation.11 The discovery of condensins that promote condensation by physically wrapping the chromatin however has provided an alternative explanation,12 which is now MedChemExpress JW 55 widely accepted. Although experiments on chromatin condensation in vitro reveal that phosphorylation of condensin I is the sole mitosis-specific modification required for the compaction of reconstituted chromatids,13,14 accumulating evidence suggests that additional components contribute to this process in vivo. One of the significant outcomes of chromatin condensation is the modulation of general gene transcription.15 Although production of some non-coding RNAs continues at the centromere,16 bulk transcription of spliced messengers is largely suppressed in mitosis and resumes at the end of cell division. Of particular importance are the condensin complexes that form and stabilize chromatin loops28 and the kinases that phosphorylate histone H3.6,7 Haspin is one of the main kinases to act on histones in early mitosis.6 It phosphorylates T3 of histone H3 producing the epigenetic mark H3T3ph, which is recognized by Survivin, a component of the chromosomal passenger complex.5,29,30 Survivin is required for the recruitment of Aurora B kinase and subsequent phosphorylation of H3S10 and H3S28.7,8,29 Small molecule inhibition of Haspin has a marked effect on early mitosis and chromosome condensation,23 but inhibition of Aurora B produces its effect only when decatenation and spindle attachment become important.31 These data agree with the idea that Haspin acts upstream of Aurora B; inhibition of the former affects phosphorylation of both H3T3 and H3S10 in vivo, but inhibition of the latter still permits H3T3ph accumulation. Mitotic H3 phosphorylation first occurs close to the pericentromeric heterochromatin and subsequently spreads out over the chromosome arms.2-4 H3K4me3, a PTM enriched at transcription start sites, has been shown to decrease Haspin activity in vitro,32-34 which may account for the delayed euchromatin condensation in vivo. The H3K9ac modification, linked to gene activation, suppresses H3 phosphorylation,35 whereas the heterochromatin-associated H3K9me3 mark does not affect in vitro catalytic activities of Haspin and Aurora B.33,34 Differential mitotic condensation of hetero- and euchromatin might have important functional consequences; whereas hardly any heterochromatin along chromosome arms is actively transcribed, 146 K. H. M. VAN WELY ET AL. delayed euchromatin condensation shortens the time without general gene transcription. Even though the spatiotemporal patterns are different, many outcomes of H3T3 and H3S10 phosphorylation at the molecular level are similar addition of a bulky negatively charged phosphate group can impede PubMed ID: the function of the adjacent methyllysine PTM. Eventually, H3T3ph and H3S10ph entirely cover the chromosomes from late prophase to metaphase. Maximum H3 phosphorylation and chromosome compaction coincide in metaphase and early anaphase,36,37 suggesting that the 2 are functionally linked in vivo. While the impor