Meiotic events at the centromeric heterochromatin: histone H3 phosphorylation, topoisomerase IIα localization and chromosome condensation

Abstract

Mechanisms of chromosome condensation and segregation during the first meiotic division are not well understood. Resolution of recombination events to form chiasmata is important, for it is chiasmata that hold homologous chromosomes together for their oppositional orientation on the meiotic metaphase spindle, thus ensuring their accurate segregation during anaphase I. Events at the centromere are also important in bringing about proper attachment to the spindle apparatus. This study was designed to correlate the presence and activity of two proteins at the centromeric heterochromatin, topoisomerase II alpha (TOP2A) and histone H3, with the processes of chromosome condensation and individualization of chiasmate bivalents in murine spermatocytes. We tested the hypothesis that phosphorylation of histone H3 is a key event instigating localization of TOP2A to the centromeric heterochromatin and condensation of chromosomes as spermatocytes exit prophase and progress to metaphase. Activity of topoisomerase II is required for condensation of chromatin at the end of meiotic prophase. Histone H3 becomes phosphorylated at the end of prophase, beginning with its phosphorylation at the centromeric heterochromatin in the diplotene stage. However, it cannot be involved in localization of TOP2A, since TOP2A is localized to the centromeric heterochromatin throughout most of meiotic prophase. This observation suggests a meiotic function for TOP2A in addition to its role in chromatin condensation. The use of kinase inhibitors demonstrates that phosphorylation of histone H3 can be uncoupled from meiotic chromosome condensation; therefore other proteins, such as those constituting metaphase-promoting factor, must be involved. These results define the timing of important meiotic events at the centromeric heterochromatin and provide insight into mechanisms of chromosome condensation for meiotic metaphase.

SUMO proteins are involved in the stress response during spermatogenesis and are localized to DNA double-strand breaks in germ cells

“…Furthermore, certain genotoxic, oxidative, and heat shock stresses rapidly increased the level of SUMO TOP1 and SUMO TOP2 conjugates (Mao et al 2000, Agostinho et al 2008. A specific role of TOP2A in germ cells has been suggested, but whether the protein's activity in these cells is regulated by sumoylation remains unknown (Cobb et al 1999). The results of this study provide evidence that such a regulation exists, and that TOP2A is sumoylated in the germ cells.…”

“…A specific topoisomerase isoform, topoisomerase 2 a (TOP2A), was abundantly expressed in germ cells, especially during meiosis (Cobb et al 1999), and the protein localization pattern partially resembled that of SUMO. As has been reported previously, in meiotic spermatocytes, SUMO localized to the inactivated sex chromosome (sex body) region ( Figure 2 Effects of stress on SUMO2/3 and SUMO1 protein expression in GC-1 spermatogonia and 15P1 Sertoli cells.…”

Prevalence of the polymorphism MTHFR A1298C and not MTHFR C677T is related to chromosomal aneuploidy in Brazilian Turner Syndrome patients

“…Besides nondisjunction, other two mechanisms can generate aneuploidies: anaphase delay, a delay in the separation of homologues or sister chromatids during anaphase (16); and a defect in the reactions mediated by methionine synthase, caused by genetic and/or dietrelated factors, leading to abnormal segregation of the chromosomes by an indirect effect of the DNA methylation patterns in the oocytes (22).…”

Impact of nucleosome dynamics and histone modifications on cell proliferation during Arabidopsis development

“…An increase in phosphorylation of histone H3 at serine 10 (H3S10ph) occurs from early prophase until telophase, a feature common to plants and animals (Hendzel et al, 1997;Cobb et al, 1999;Houben et al, 1999). Phosphorylation of other residues of H3, typically, T3, T11 and S28, also occurs during mitosis and meiosis (Houben et al, 2007).…”