Essential role of paternal chromatin in the regulation of transcriptional activity during mouse preimplantation development
Essential role of paternal chromatin in the regulation of transcriptional activity during mouse preimplantation development
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DOI：
10.1530/rep-10-0109
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发表时间：
2011-01-01
期刊：
影响因子：
3.8
通讯作者：
Wakayama, Teruhiko
中科院分区：
文献类型：
--
作者：
Bui, Hong-Thuy;Wakayama, Sayaka;Wakayama, Teruhiko
一些证据表明，在植入前的小鼠胚胎中，两细胞阶段转录抑制状态的形成叠加在胚胎基因组的激活上。然而，在这一阶段很难确定新合成的(新生)RNA的轮廓，因为大量母体RNA积累在成熟的卵母细胞中以支持早期发育。利用5-溴-5‘-三磷酸标记的RNA，我们证实了在正常受精的胚胎中，新生的RNA合成在2-细胞和4-细胞的过渡期间受到抑制，而在孤雌胚胎中则没有。此外，这种抑制是由精子(男性)染色质贡献的，我们通过研究雄核发育胚胎证实了这一点。利用精子发育的不同阶段，研究了抑制新生RNA产生的因素的来源。与未成熟的圆形精子细胞受精相比，ICSI组在两细胞阶段的转录活性较低，这与ICSI组在四细胞阶段的进一步抑制相一致。最后，用标记的组蛋白H3和H4进行DNA复制和染色质重塑的研究，以区分男性和女性原核。雄性和雌性染色质的结合似乎减少了受精胚胎中新生RNA的产生。这项研究表明，父系染色质在小鼠着床前发育过程中转录活性的调节中起着重要作用，而且这种能力是在精子发生过程中获得的。生殖(2011)141 67-77
Several lines of evidence indicate that the formation of a transcriptionally repressive state during the two-cell stage in the preimplantation mouse embryo is superimposed on the activation of the embryonic genome. However, it is difficult to determine the profile of newly synthesized (nascent) RNA during this phase because large amounts of maternal RNA accumulate in maturing oocytes to support early development. Using 5-bromouridine-5'-triphosphate labeling of RNA, we have verified that nascent RNA synthesis was repressed between the two-cell and four-cell transition in normally fertilized but not in parthenogenetic embryos. Moreover, this repression was contributed by sperm (male) chromatin, which we confirmed by studying androgenetic embryos. The source of factors responsible for repressing nascent RNA production was investigated using different stages of sperm development. Fertilization with immature round spermatids resulted in a lower level of transcriptional activity than with ICSI at the two-cell stage, and this was consistent with further repression at the four-cell stage in the ICSI group. Finally, study on DNA replication and chromatin remodeling was performed using labeled histones H3 and H4 to differentiate between male and female pronuclei. The combination of male and female chromatin appeared to decrease nascent RNA production in the fertilized embryo. This study indicates that paternal chromatin is important in the regulation of transcriptional activity during mouse preimplantation development and that this capacity is acquired during spermiogenesis. Reproduction (2011) 141 67-77