Large-scale DNA demethylation occurs in proliferating ovarian granulosa cells during mouse follicular development.
Large-scale DNA demethylation occurs in proliferating ovarian granulosa cells during mouse follicular development.
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DOI：
10.1038/s42003-021-02849-w
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发表时间：
2021-11-25
影响因子：
5.9
通讯作者：
Shimada M
中科院分区：
文献类型：
--
作者：
Kawai T;Richards JS;Shimada M
在卵巢卵泡发育过程中，颗粒细胞增殖并逐渐分化以支持卵母细胞成熟和排卵。为了确定颗粒细胞增殖和分化之间的潜在联系，我们确定了1)调节DNA甲基化的基因表达和2)DNA甲基化模式、组蛋白乙酰化水平和基因组DNA结构的变化。马绒毛膜促性腺激素（eCG）作用后，s期颗粒细胞增殖增加，DNA甲基转移酶（DNMT1）显著降低，Tet甲基胞嘧啶双加氧酶2 （TET2）显著升高。综合MeDIP-seq分析表明，eCG治疗降低了颗粒细胞中约40%基因启动子区域的甲基化。特异性去甲基化基因的表达显著增加，与特异性组蛋白修饰和DNA结构的变化相关。这些表观遗传过程被细胞周期抑制剂抑制。基于这些结果，我们提出连续表观遗传事件的时间对颗粒细胞分化的渐进式、阶级式变化至关重要。Tomoko Kawai等人研究了颗粒细胞分化和增殖过程中的DNA甲基化模式。他们的结果表明，连续的表观遗传事件对于颗粒细胞分化的进行性变化是必不可少的。
During ovarian follicular development, granulosa cells proliferate and progressively differentiate to support oocyte maturation and ovulation. To determine the underlying links between proliferation and differentiation in granulosa cells, we determined changes in 1) the expression of genes regulating DNA methylation and 2) DNA methylation patterns, histone acetylation levels and genomic DNA structure. In response to equine chorionic gonadotropin (eCG), granulosa cell proliferation increased, DNA methyltransferase (DNMT1) significantly decreased and Tet methylcytosine dioxygenase 2 (TET2) significantly increased in S-phase granulosa cells. Comprehensive MeDIP-seq analyses documented that eCG treatment decreased methylation of promoter regions in approximately 40% of the genes in granulosa cells. The expression of specific demethylated genes was significantly increased in association with specific histone modifications and changes in DNA structure. These epigenetic processes were suppressed by a cell cycle inhibitor. Based on these results, we propose that the timing of sequential epigenetic events is essential for progressive, stepwise changes in granulosa cell differentiation. Tomoko Kawai et al. investigate DNA methylation patterns during granulosa cell differentiation and proliferation. Their results suggest that sequential epigenetic events are essential for progressive changes in granulosa cell differentiation.
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影响因子：
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作者：
Gong Y;Li-Ling J;Xiong D;Wei J;Zhong T;Tan H
通讯作者：
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影响因子：
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Curry, Thomas E., Jr.
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通讯作者：
Noble WS
影响因子：
16.6
作者：
Bell, J. T.;Loomis, A. K.;Butcher, L. M.;Gao, F.;Zhang, B.;Hyde, C. L.;Sun, J.;Wu, H.;Ward, K.;Harris, J.;Scollen, S.;Davies, M. N.;Schalkwyk, L. C.;Mill, J.;Williams, F. M. K.;Li, N.;Deloukas, P.;Beck, S.;McMahon, S. B.;Wang, J.;John, S. L.;Spector, T. D.
通讯作者：
Spector, T. D.