Abnormal clones in Philadelphia negative (Ph-) cells in CML patients treated with Imatinib mesylate

Mammalian histone variant H3.3 differs from replication-dependent histone H3.1 by five amino acids, including replacement of alanine 31 by serine. H3.3 is expressed throughout the cell cycle, primarily deposited at transcriptionally active loci independent of S-phase. Data from mammalian cells suggest that phosphorylation of serine 31 (H3.3S31P) plays a role in mitosis. Here we show that H3.3S31P also occurs during mitosis of the urochordate Oikopleura dioica, suggesting this histone modification and its function in mitosis is already present at the invertebrate-vertebrate transition. The spatial pattern differed from that of H3 phosphorylation at serine 28 (H3S28P). H3S28P was enriched near telomeric regions, but H3.3S31P differed both temporally and spatially from the mammalian pattern, being more widely distributed throughout prophase, prometaphase and metaphase chromosomes. We also identified an important role for H3.3S31P during oogenic meiosis in the semelparous O. dioica. H3.3S31P initiated together with H3S28P in all meiotic nuclei in late diplotene, after H3S10P. However, H3.3S31P was retained only on the subset of meiotic nuclei that seeded maturing oocytes and proceeded through meiosis to arrest in metaphase I. Thus, this epigenetic mark is part of a regulatory circuitry that enables O. dioica to numerically adjust oocyte production over two orders of magnitude.