Compensatory functions of histone deacetylase 1 (HDAC1) and HDAC2 regulate transcription and apoptosis during mouse oocyte development
Compensatory functions of histone deacetylase 1 (HDAC1) and HDAC2 regulate transcription and apoptosis during mouse oocyte development
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DOI：
10.1073/pnas.1118403109
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发表时间：
2012-02-21
影响因子：
11.1
通讯作者：
Schultz, Richard M.
中科院分区：
文献类型：
--
作者：
Ma, Pengpeng;Pan, Hua;Schultz, Richard M.
在卵母细胞生长过程中，染色质结构和组蛋白修饰发生了巨大的变化，以及转录的全局停止。组蛋白修饰在这些过程中的作用尚不清楚。我们报道了有条件地删除Hdac1和Hdac2对卵母细胞发育的影响。删除任何一个基因对卵母细胞发育几乎没有影响，而删除两个基因会导致卵泡发育在次级卵泡阶段停滞。这种发育停滞伴随着转录组的大量扰动和转录的整体减少，即使组蛋白乙酰化显着增加。组蛋白抑制标记没有明显变化，但组蛋白H3K4甲基化（一个激活标记）明显减少。H3K4甲基化的减少可能是Kdm5b表达增加的结果，因为rnai介导的双突变卵母细胞中Kdm5b的靶向导致H3K4甲基化增加。TRP53乙酰化的增加也发生在突变的卵母细胞中，并可能导致观察到的细胞凋亡发生率增加。综上所述，这些结果表明组蛋白和非组蛋白乙酰化在卵母细胞发育中的重要作用。
Dramatic changes in chromatin structure and histone modification occur during oocyte growth, as well as a global cessation of transcription. The role of histone modifications in these processes is poorly understood. We report the effect of conditionally deleting Hdac1 and Hdac2 on oocyte development. Deleting either gene has little or no effect on oocyte development, whereas deleting both genes results in follicle development arrest at the secondary follicle stage. This developmental arrest is accompanied by substantial perturbation of the transcriptome and a global reduction in transcription even though histone acetylation is markedly increased. There is no apparent change in histone repressive marks, but there is a pronounced decrease in histone H3K4 methylation, an activating mark. The decrease in H3K4 methylation is likely a result of increased expression of Kdm5b because RNAi-mediated targeting of Kdm5b in double-mutant oocytes results in an increase in H3K4 methylation. An increase in TRP53 acetylation also occurs in mutant oocytes and may contribute to the observed increased incidence of apoptosis. Taken together, these results suggest seminal roles of acetylation of histone and nonhistone proteins in oocyte development.