Histone Phosphorylation and Pericentromeric Histone Modifications in Oocyte Meiosis

Abstract

Epigenetic regulation of pericentromeric heterochromatin is crucial for proper interactions between kinetochores and spindle microtubules governing accurate chromosome segregation. Here, we first examined the dynamic distribution of phosphorylated serine 10 and 28 on H3 during mouse oocyte maturation and early embryo development using immunofluorescent staining and confocal microscopy. Our results revealed strong signals of phosphorylated H3/ser10 and 28 in the pericentromeric heterochromatin area and continuous persistent staining of the chromosome periphery, respectively. A panel of specific antibodies against various acetylated lysine, dimethylated lysine or phosphorylated serine residues on histone H3 or H4 were used to investigate the effects of Trichostatin A (TSA), a general inhibitor of histone deacetylases (HDACs), on histone modifications of pericentromeric heterochromatin. Unexpectedly, TSA treatment was unable to alter the acetylation and methylation status of pericentromeric heterochromatin, however, it resulted in significant dephosphorylation of H3/ser10 at this site during mouse oocyte meiosis, which is likely to play a role in the TSA-induced defective chromosome segregation. Furthermore, by using ZM447439, an inhibitor of Aurora kinases, we revealed that Aurora kinases may participate in the regulation of histone phosphorylation during mouse oocyte maturation.

Histone modifications during mammalian oocyte maturation: Dynamics, regulation and functions

“…34 Interestingly, we found that inhibition of Aurora kinase significantly decreased the phosphorylation levels of both H3/ Ser10 and H3/Ser28 in mouse oocyte, resulting in chromosome misalignment. 31 These observations suggest that Aurora kinase participates in the regulation of histone H3 phosphorylation during oocyte meiosis, which may be essential for the correct chromosome alignment and segregation. On the other hand, the phosphatase that dephosphorylates H3/Ser10 has been identified as protein phosphasetase 1 (PP1) in budding yeast and nematodes.…”

“…2). 31 At GV stage, staining of H3/Ser28ph was barely observed on chromatin. Upon meiotic resumption, H3/Ser28ph was clearly detectable at the periphery of Pre-MI chromosomes, and this distribution pattern was maintained until MII.…”

“…Importantly, TSA treatment significantly resulted in the dephosphorylation of histone H3/Ser10 in this region. 31 Similarly, addition of histone deacetylase inhibitors prior to the end of S-phase resulted in a decrease of phosphorylation at pericentromeric histone H3 in G 2 phase in two human tumor cell lines. 95 These data suggest that dephosphorylation of H3/Ser10 may be responsible, at least in part, for TSA-induced defective chromosome segregation.…”

Progesterone receptor membrane component 1 expression and putative function in bovine oocyte maturation, fertilization, and early embryonic development

“…It gradually becomes phosphorylated on threonine 232 (Thr232) during oocyte maturation. Phosphorylation of AURKB activates this kinase and leads to the phosphorylation of histone H3 and the gradual condensation of chromatin (Jelinkova & Kubelka 2006, Wang et al 2006, Swain et al 2008. Moreover, altered AURKB activity increases the risk in chromosome congression failure, nondysjunction, and aneuploidy in mammalian oocytes (Vogt et al 2009).…”

Phospho-Signaling at Oocyte Maturation and Fertilization: Set Up for Embryogenesis and Beyond Part II. Kinase Regulators and Substrates

“…Posttranslational modifications such as acetylation, methylation, and phosphorylation regulate the DNA-binding property of histones including H3. In some mammalian species, phosphorylation of H3 by aurora kinase and an adjacent dimethylated lysine residue are coordinately involved in chromosomal condensation during oocyte maturation (Bui et al 2007;Ding et al 2011;Eberlin et al 2008;Gu et al 2008;Jelinkova and Kubelka 2006;Maton et al 2003;Swain et al 2007;Wang et al 2006). …”