Role of CxxC-finger protein 1 in establishing mouse oocyte epigenetic landscapes.
Role of CxxC-finger protein 1 in establishing mouse oocyte epigenetic landscapes.
复制标题
CxxC-finger 蛋白 1 在建立小鼠卵母细胞表观遗传景观中的作用
DOI：
10.1093/nar/gkab107
复制
发表时间：
2021-03-18
影响因子：
14.9
通讯作者：
Fan HY
中科院分区：
文献类型：
--
作者：
Sha QQ;Zhu YZ;Xiang Y;Yu JL;Fan XY;Li YC;Wu YW;Shen L;Fan HY
在卵发生过程中，卵母细胞获得能力，随后经历减数分裂成熟，为胚胎发育做准备；赖氨酸-4上的三甲基化组蛋白H3 （H3K4me3）在这些过程中介导了广泛的核事件。卵母细胞特异性敲除cxxc -指蛋白1 （CXXC1，也称为CFP1）会损害H3K4me3的积累并导致染色质构型的改变。本研究探讨了Cxxc1基因敲除后卵母细胞基因组H3K4me3图谱的变化及其对DNA甲基化、H3K27me3、H2AK119ub1和H3K36me3等其他表观遗传因素的影响。敲除Cxxc1后，H3K4me3整体减少，包括启动子区域和基因体。CXXC1和MLL2（另一种组蛋白H3甲基转移酶）在卵子发生过程中介导H3K4三甲基化的作用不重叠。Cxxc1缺失导致DNA甲基化水平下降，影响H3K27me3和H2AK119ub1的分布，特别是在DNA甲基化水平高的区域。Cxxc1缺失导致的表观遗传网络变化与相应基因组区域基因的转录变化相关。本研究阐明了缺失Cxxc1的卵母细胞表型和分子缺陷背后的表观遗传变化，并强调了Cxxc1在协调多个因素中所起的作用，这些因素参与了建立母体基因组适当的表观遗传状态。
Abstract During oogenesis, oocytes gain competence and subsequently undergo meiotic maturation and prepare for embryonic development; trimethylated histone H3 on lysine-4 (H3K4me3) mediates a wide range of nuclear events during these processes. Oocyte-specific knockout of CxxC-finger protein 1 (CXXC1, also known as CFP1) impairs H3K4me3 accumulation and causes changes in chromatin configurations. This study investigated the changes in genomic H3K4me3 landscapes in oocytes with Cxxc1 knockout and the effects on other epigenetic factors such as the DNA methylation, H3K27me3, H2AK119ub1 and H3K36me3. H3K4me3 is overall decreased after knocking out Cxxc1, including both the promoter region and the gene body. CXXC1 and MLL2, which is another histone H3 methyltransferase, have nonoverlapping roles in mediating H3K4 trimethylation during oogenesis. Cxxc1 deletion caused a decrease in DNA methylation levels and affected H3K27me3 and H2AK119ub1 distributions, particularly at regions with high DNA methylation levels. The changes in epigenetic networks implicated by Cxxc1 deletion were correlated with the transcriptional changes in genes in the corresponding genomic regions. This study elucidates the epigenetic changes underlying the phenotypes and molecular defects in oocytes with deleted Cxxc1 and highlights the role of CXXC1 in orchestrating multiple factors that are involved in establishing the appropriate epigenetic states of maternal genome.
登录
查看更多内容
影响因子：
14.9
作者：
Gatchalian J;Gallardo CM;Shinsky SA;Ospina RR;Liendo AM;Krajewski K;Klein BJ;Andrews FH;Strahl BD;M van Wely KH;Kutateladze TG
通讯作者：
Kutateladze TG
影响因子：
4.1
作者：
LaVoie, HA
通讯作者：
LaVoie, HA
影响因子：
4.8
作者：
Lee, JH;Skalnik, DG
通讯作者：
Skalnik, DG
影响因子：
16.6
作者：
Brind'Amour, Julie;Liu, Sheng;Lorincz, Matthew C.
通讯作者：
Lorincz, Matthew C.
影响因子：
9.2
作者：
Lewandoski, M;Wassarman, KM;Martin, GR
通讯作者：
Martin, GR