Stage specific expression of histone deacetylase 4 (HDAC4) during oogenesis and early preimplantation development in mice
Stage specific expression of histone deacetylase 4 (HDAC4) during oogenesis and early preimplantation development in mice
复制标题
DOI：
10.1262/jrd.17044
复制
发表时间：
2006-02-01
影响因子：
1.8
通讯作者：
Aoki, F
中科院分区：
文献类型：
--
作者：
Kageyama, S;Liu, HL;Aoki, F
卵子发生是配子形成的关键事件，配子将基因组信息传递给下一代。在此过程中，基因表达模式随着基因组重塑而发生巨大变化，而基因组信息却保持稳定。组蛋白乙酰化的水平在卵子发生过程中发生巨大变化，与基因组重塑的调节有关。为了鉴定参与卵子发生过程中组蛋白乙酰化水平动态变化的基因，我们使用未受精卵母细胞与受精卵母细胞进行了抑制性消减杂交（SSH）。在 SSH 识别的基因中，我们发现了组蛋白脱乙酰酶 4 (HDAC4)，其表达仅在少数类型的成体组织中检测到。 RT-PCR 分析表明，HDAC4 的表达对于成熟的卵母细胞具有特异性。 HDAC4 转录物在生长的卵母细胞中几乎检测不到，而在完全生长的卵母细胞中很容易检测到。表达量一直维持在高水平直至MII阶段，但在受精后显着下降。然后，表达水平保持较低水平直至桑葚胚阶段。免疫细胞化学将 HDAC4 蛋白定位于完全生长的卵母细胞的染色体中。尽管由于染色质核心组蛋白的脱乙酰化，HDAC 与转录调控关系最为密切，但之前的研究表明，所有检查的组蛋白残基在成熟的卵母细胞中都高度乙酰化。因此，我们的结果表明 HDAC4 作用于非组蛋白，并在成熟卵母细胞的一些其他细胞功能中发挥作用。为了解决这种可能性，我们检查了 p53BP1 的表达，它与 HDAC4 相关，在 DNA 损伤反应中发挥着关键作用。 RT-PCR 分析表明，p53BP1 在完全生长的卵母细胞中特异性表达，HDAC4 也是如此。这些结果表明 HDAC4 在稳定完全生长的卵母细胞基因组方面发挥着作用。
Oogenesis is a critical event in the formation of gametes, which transfer genomic information to the next generation. During this process, the gene expression pattern changes dramatically concomitant with genome remodeling, while the genomic information is stably maintained. Histone acetylation, the level of which is dramatically changed during oogenesis, has been implicated in the regulation of genome remodeling. In order to identify genes that are involved in the dynamic changes in histone acetylation levels during oogenesis, we performed suppressive subtraction hybridization (SSH) using unfertilized versus fertilized oocytes. Among the genes identified by SSH, we found histone deacetylase 4 (HDAC4), whose expression has been detected in only a few types of adult tissues. RT-PCR analysis revealed that the expression of HDAC4 was specific for full-grown oocytes. The HDAC4 transcript was barely detected in the growing oocytes, whereas it was readily detectable in fully grown oocytes. The expression was maintained at a high level until the MII stage, but decreased prominently after fertilization. Then, the expression level remained low until the morula stage. Immunocytochemistry localized the HDAC4 protein in the chromosome of fully grown oocytes. Although HDACs are most closely linked with transcriptional regulation owing to deacetylation of the core histones of the chromatin, previous studies have shown that all of the histone residues examined were highly acetylated in full-grown oocytes. Therefore, our results suggest that HDAC4 acts on a non-histone protein and plays a role in some other cellular functions of full-grown oocytes. To address this possibility, we examined the expression of p53BP1, which is associated with HDAC4 and plays a critical role in the DNA damage response. RT-PCR analysis revealed that p53BP1 was expressed specifically in fully grown oocytes, as was HDAC4. These results suggest that HDAC4 plays a role in stabilizing the genomes of fully grown oocytes.