同型半胱氨酸对卵母细胞发育过程中组蛋白甲基化和乙酰化的影响
the effect of homocysteine on histone methlytion and acetylation during oocyte development
目的:了解卵母细胞发育过程中同型半胱氨酸对组蛋白表观遗传修饰的影响。方法:首先HCY作用于完整卵泡的体外培养体系,在卵母细胞早期发育过程中利用细胞免疫组化的方法观察HCY对代表性的甲基化组蛋白H3K4、H3K9以及乙酰化组蛋白H3K9分布的影响;其次利用卵母细胞的体外成熟培养体系,观察HCY对卵母细胞成熟过程的影响,通过实时定量PCR的方法,观察在此成熟过程中HCY对卵母细胞内组蛋白乙酰化水平的调控酶GCN5和HDAC表达的影响。结果:HCY明显抑制卵母细胞的体外成熟,HCY作用下,甲基化组蛋白H3K4、H3K9以及乙酰化组蛋白H3K9的分布没有变化但是表达的强度降低,核呈现去浓缩的趋势,成熟过程中HCY并不改变基因GCN5的表达水平,却明显抑制卵母细胞内HDAC基因的表达。结论:卵母细胞发育过程中高水平的同型半胱氨酸影响组蛋白的表观遗传修饰,HCY对卵母细胞核内组蛋白甲基化和乙酰化的影响有可能是造成核染色体稳定性下降的重要原因。
Objective: To understand the effect of homocysteine on histone modification during oocyte development. Method: In this paper the follicle culture system and method of oocyte maturated in vitro were used and the process of oocyte development and maturation was observed. By immunofluorescent staining the influence of HCY on distribution of methylated histone H3K4, H3K9, and acetylated histone H3K9 during early stage of oocyte development was observed. And with the approach of real time PCR, the expression level of two enzymes controlling histone acetylation, histone deacetylase(HDAC) and histone acetyltransferase (GCN5), in oocyte maturated in vitro was compared between group coculture with homocysteine and control. Results: The process of oocyte maturation was significantly inhibited by homocysteine. Though the distribution patterns of methylated histone H3K4, H3K9 and acetylated histone H3K9, the staining intensity was decreased by homocysteine.The chromatin reveals slightly decondensated. The influence of HCY on GCN5 expression was tiny, but the expression of HDAC in oocyte was significantly inhibited.Conclusion: The effect of homocysteine on histone methylation and acetylation was indeed present during oocyte development. This may be the good reason for the decline of nuclear chromosome stability caused by homocysteine.
石程、陈曦、张育军、梁蓉
基础医学生物化学生理学
卵母细胞发育同型半胱氨酸组蛋白甲基化组蛋白乙酰化
oocyte developmenthomocysteinehistone methylationhistone acetylation
石程,陈曦,张育军,梁蓉.同型半胱氨酸对卵母细胞发育过程中组蛋白甲基化和乙酰化的影响[EB/OL].(2011-12-22)[2025-08-02].http://www.paper.edu.cn/releasepaper/content/201112-593.点此复制
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