Regulation of histone acetylation during meiotic maturation in mouse oocytes
Regulation of histone acetylation during meiotic maturation in mouse oocytes
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DOI：
10.1002/mrd.20121
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发表时间：
2004-10-01
影响因子：
2.5
通讯作者：
Aoki, F
中科院分区：
文献类型：
--
作者：
Akiyama, T;Kim, JM;Aoki, F
组蛋白乙酰化是一种重要的表观遗传修饰，涉及染色质结构的调节以及随后的基因表达。在小鼠卵母细胞减数分裂过程中，组蛋白整体去乙酰化，但没有有丝分裂。这种减数分裂特异性脱乙酰化的调节尚未阐明。在这里，我们证明，p34（cdc 2）激酶活性和蛋白质合成负责组蛋白脱乙酰酶的激活和组蛋白乙酰转移酶（HAT）的抑制，分别导致组蛋白H4在赖氨酸12（H4 K12）在小鼠卵母细胞减数分裂过程中的脱乙酰化。使用乙酰化H4 K12的特异性抗体，在减数分裂成熟过程中用免疫细胞化学方法检查H4 K12乙酰化状态的时间变化。H4 K12在第一次减数分裂期间被脱乙酰化，在第一极体（PB 1）挤出时暂时乙酰化，然后在第二次减数分裂期间再次脱乙酰化。由于这些变化与已知的p34（cdc 2）激酶活性的振荡模式相吻合，我们研究了该激酶参与H4 K12去乙酰化。Roscovitine，一种细胞周期蛋白依赖性激酶活性的抑制剂，在第一次和第二次减数分裂期间阻止了H4 K12的脱乙酰化，这表明在减数分裂期间脱乙酰化需要p34（cdc 2）激酶活性。此外，放线菌酮，蛋白质合成抑制剂，也阻止脱乙酰化。在PB 1挤出后，此时H4 K12已被脱乙酰化，通过用放线菌酮处理而不是用roscovitine处理，H4 K12在凝聚的染色体中被再乙酰化。这些结果表明HAT存在，但被新合成的不参与p34（cdc 2）激酶活性的蛋白质灭活。我们的研究结果表明，p34（cdc 2）激酶活性诱导H4 K12的脱乙酰化和脱乙酰化状态是由新合成的蛋白质，抑制HAT活性在减数分裂过程中维持。(C)2004 Wiley-Liss，Inc.
Histone acetylation is an important epigenetic modification implicated in the regulation of chromatin structure and, subsequently, gene expression. Global histone deacetylation was reported in mouse oocytes during meiosis but not mitosis. The regulation of this meiosis-specific deacetylation has not been elucidated. Here, we demonstrate that p34(cdc2) kinase activity and protein synthesis are responsible for the activation of histone deacetylases and the inhibition of histone acetyltransferases (HATs), respectively, resulting in deacetylation of histone H4 at lysine12 (H4K12) during mouse oocyte meiosis. Temporal changes in the acetylation state of H4K12 were examined immunocytochemically during meiotic maturation using an antibody specific for acetylated H4K12. H4K12 was deacetylated during the first meiosis, temporarily acetylated around the time of the first polar body (PBl) extrusion, and then deacetylated again during the second meiosis. Because these changes coincided with the known oscillation pattern of p34(cdc2) kinase activity, we investigated the involvement of the kinase in H4K12 deacetylation. Roscovitine, an inhibitor of cyclin-dependent kinase activity, prevented H4K12 deacetylation during both the first and second meiosis, suggesting that p34(cdc2) kinase activity is required for deacetylation during meiosis. In addition, cycloheximide, a protein synthesis inhibitor, also prevented deacetylation. After PB1 extrusion, at which time H4K12 had been deacetylated, H4K12 was re-acetylated in the condensed chromosomes by treatment with cycloheximide but not with roscovitine. These results demonstrate that HATs are present but inactivated by newly synthesized protein(s) that is (are) not involved in p34(cdc2) kinase activity. Our results suggest that p34(cdc2) kinase activity induces the deacetylation of H4K12 and that the deacetylated state is maintained by newly synthesized protein(s) that inhibits HAT activity during meiosis. (C) 2004 Wiley-Liss, Inc.