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Cell Rep:浙江大学范衡宇研究组报道表观遗传因子CXXC1在卵子成熟和早期胚胎发育中的功能

摘要 : 2017年8月1日,国际著名学术杂志《Cell》子刊《Cell Reports》杂志在线发表了浙江大学生命科学研究院范衡宇研究组题为“CFP1 Regulates Histone H3K4 Trimethylation and Developmental Potential in Mouse Oocytes”。

2017年8月1日,国际著名学术杂志《Cell》子刊《Cell Reports》杂志在线发表了浙江大学生命科学研究院范衡宇研究组题为“CFP1 Regulates Histone H3K4 Trimethylation and Developmental Potential in Mouse Oocytes”。

表观遗传学修饰是调控细胞分化过程的主要机制之一,表观遗传学调控在生殖细胞中尤为重要。受精过程中,合子DNA在卵母细胞中母源性因子的作用下发生重编程,促进合子基因组的重编程和转录激活,因此受精卵基因组重编程过程是表观遗传因子调控机制的理想模型,但调节机制很少被研究过。在辅助生殖临床实践中,有些成熟的卵母细胞受精以后不能启动正常的胚胎发育,很可能是由于基因组重编程过程的缺陷造成的。

 

DNA结合蛋白CxxC finger protein-1 (CXXC1)是SET1组蛋白甲基化复合体中的重要亚基,介导特定染色体区域组蛋白H3的第4位赖氨酸发生3甲基化(H3K4me3),负责大量基因的转录调控。目前CXXC1的重要生理功能才刚刚被认识,缺少体内功能研究。浙江大学生命科学研究院范衡宇课题组制作了卵母细胞特异性的Cxxc1敲除小鼠,发现CXXC1对于卵母细胞和受精卵的基因组重编程尤其关键。CXXC1在小鼠卵母细胞中优势表达,在卵母细胞中敲除Cxxc1造成卵母细胞发育异常,不具备进一步发育的潜能,导致胚胎发育一细胞到二细胞期阻滞。转录组学研究表明,许多与卵母细胞成熟和受精卵发育激活相关的基因在Cxxc1敲除以后不能正常表达。本研究表明,CXXC1介导的组蛋白H3K4三甲基化修饰是生殖细胞表观遗传成熟的重要方面。

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原文链接:

CFP1 Regulates Histone H3K4 Trimethylation and Developmental Potential in Mouse Oocytes

原文摘要:

Trimethylation of histone H3 at lysine-4 (H3K4me3) is associated with eukaryotic gene promoters and poises their transcriptional activation during development. To examine the in vivo function of H3K4me3 in the absence of DNA replication, we deleted CXXC finger protein 1 (CFP1), the DNA-binding subunit of the SETD1 histone H3K4 methyltransferase, in developing oocytes. We find that CFP1 is required for H3K4me3 accumulation and the deposition of histone variants onto chromatin during oocyte maturation. Decreased H3K4me3 in oocytes caused global downregulation of transcription activity. Oocytes lacking CFP1 failed to complete maturation and were unable to gain developmental competence after fertilization, due to defects in cytoplasmic lattice formation, meiotic division, and maternal-zygotic transition. Our study highlights the importance of H3K4me3 in continuous histone replacement for transcriptional regulation, chromatin remodeling, and normal developmental progression in a non-replicative system.

来源: Cell Reports 浏览次数:0

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