Histone phosphorylation and pericentromeric histone modifications in oocyte meiosis.
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.
Wang
Qiang
Q
State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
Wang
Chun-Min
CM
Ai
Jun-Shu
JS
Xiong
Bo
B
Yin
Shen
S
Hou
Yi
Y
Chen
Da-Yuan
DY
Schatten
Heide
H
Sun
Qing-Yuan
QY
D000107:Acetylation; D000818:Animals; D064127:Aurora Kinases; D001755:Blastocyst / Q000201:enzymology; D002503:Centromere; D020090:Chromosome Segregation; D047108:Embryonic Development; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006570:Heterochromatin / Q000187:drug effects / Q000201:enzymology*; D056572:Histone Deacetylase Inhibitors; D006657:Histones / Q000737:chemistry / Q000378:metabolism*; D006877:Hydroxamic Acids / Q000494:pharmacology; D008540:Meiosis; D008745:Methylation; D051379:Mice; D018613:Microscopy, Confocal; D009865:Oocytes / Q000187:drug effects / Q000201:enzymology / Q000254:growth & development*; D010766:Phosphorylation / Q000187:drug effects; D010768:Phosphoserine / Q000032:analysis; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism
D004791:Enzyme Inhibitors; D006570:Heterochromatin; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D006877:Hydroxamic Acids; D010768:Phosphoserine; C012589:trichostatin A; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases