Hira-mediated H3.3 incorporation is required for DNA replication and ribosomal RNA transcription in the mouse zygote.

Hira-mediated H3.3 incorporation is required for DNA replication and ribosomal RNA transcription in the mouse zygote.
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DOI:
10.1016/j.devcel.2014.06.022
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发表时间:
2014-08-11
期刊:
影响因子:
11.8
通讯作者:
Ramalho-Santos, Miguel
Ramalho-Santos, Miguel
中科院分区:
生物学1区
文献类型:
--
作者:
Lin, Chih-Jen;Koh, Fong Ming;Wong, Priscilla;Conti, Marco;Ramalho-Santos, Miguel

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广泛的染色质重编程发生在受精时,被认为是在母体因素的控制下,但其潜在的机制仍然知之甚少。我们报告说,母亲希拉,组蛋白变体H3.3的伴侣,是需要小鼠发育过去的受精卵阶段。由于精子基因组中缺乏核小体组装,Hira缺失后,雄性原核的形成受到抑制。Hira突变的卵母细胞不能孤雌发育,表明Hira在雌性基因组中的作用。两个亲本基因组都显示突变体中DNA复制和转录水平高度降低。长期以来,人们一直认为转录不是合子发育所必需的。令人惊讶的是,我们发现,Hira/H3.3依赖的核糖体RNA的转录是第一次切割所必需的。我们的研究结果表明,Hira介导的H3.3掺入是必不可少的父母的基因组重编程,并揭示了一个意想不到的作用rRNA转录在小鼠受精卵。
Extensive chromatin reprogramming occurs at fertilization and is thought to be under the control of maternal factors, but the underlying mechanisms remain poorly understood. We report that maternal Hira, a chaperone for the histone variant H3.3, is required for mouse development past the zygote stage. Male pronucleus formation is inhibited upon deletion of Hira due to a lack of nucleosome assembly in the sperm genome. Hira mutant oocytes are incapable of developing parthenogenetically, indicative of a role for Hira in the female genome. Both parental genomes show highly reduced levels of DNA replication and transcription in the mutants. It has long been thought that transcription is not required for zygote development. Surprisingly, we found that Hira/H3.3-dependent transcription of ribosomal RNA is required for first cleavage. Our results demonstrate that Hira-mediated H3.3 incorporation is essential for parental genome reprogramming, and reveal an unexpected role for rRNA transcription in the mouse zygote.
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