Transgenerational propagation and quantitative maintenance of paternal centromeres depends on Cid/Cenp-A presence in Drosophila sperm.
Transgenerational propagation and quantitative maintenance of paternal centromeres depends on Cid/Cenp-A presence in Drosophila sperm.
复制标题
DOI：
10.1371/journal.pbio.1001434
复制
发表时间：
2012
期刊：
影响因子：
9.8
通讯作者：
Lehner CF
中科院分区：
文献类型：
--
作者：
Raychaudhuri N;Dubruille R;Orsi GA;Bagheri HC;Loppin B;Lehner CF
对果蝇精子中着丝粒特异性组蛋白CenH3水平经实验改变后的子代着丝粒进行分析，揭示了这种表观遗传标记的数量遗传。
在黑腹果蝇中，如同在许多动植物物种中一样，着丝粒的特性是由表观遗传决定的。在增殖细胞中，一种着丝粒特异性组蛋白H3变体（CenH3），在果蝇中称为Cid，在人类中称为Cenp - A，是表观遗传着丝粒标记的关键组成部分。因此，在有丝分裂增殖过程中维持CenH3的数量和染色体位置是很重要的。有趣的是，CenH3在减数分裂和胚胎发生起始过程中可能具有不同的作用。在秀丽隐杆线虫的配子中，并且可能在植物中，着丝粒标记不依赖于CenH3。此外，动物雄性配子分化通常包括组蛋白与鱼精蛋白的整体交换，这可能会去除CenH3核小体。在此我们证明，雄性减数分裂过程中Cid的装载调控与早期胚胎发生的有丝分裂周期中所观察到的调控不同。但是Cid存在于成熟精子中。在精子中Cid严重缺失后，父本着丝粒无法整合到第一次有丝分裂的单倍体纺锤体中，导致孤雌生殖单倍体胚胎。此外，在适度缺失后，父本着丝粒在下一世代无法重新获得正常的Cid水平。我们得出结论，精子中的Cid是父本染色体上表观遗传着丝粒标记的重要组成部分，并且在整个发育过程中对着丝粒Cid水平进行数量调控。因此，每个细胞周期中装载的Cid数量似乎主要由预先存在的着丝粒Cid决定，对于意外损失的补偿灵活性很小。
真核细胞中的遗传信息被分割到染色体中。这些信息链在有丝分裂和减数分裂细胞分裂过程中精确地传递给子细胞，但前提是着丝粒（一个特殊的染色体区域）具有功能。包括人类和果蝇黑腹果蝇在内的许多物种染色体中的着丝粒区域被认为是通过掺入一种着丝粒特异性组蛋白H3变体（CenH3）由表观遗传决定的。在染色体复制后，产生的两条姐妹染色单体中的着丝粒可能预期是由在复制过程中均匀分布在两个拷贝上的预先存在的CenH3和以化学计量方式由分配池招募的新CenH3的混合物组成。在此，我们通过实验改变果蝇精子中着丝粒CenH3的水平来探究着丝粒是否确实以这种方式复制。我们表明，在由缺乏CenH3的精子受精的胚胎中，父本染色体上的着丝粒无法招募新的CenH3。通过使用着丝粒CenH3含量增加或减少的精子，我们证明改变的CenH3水平在子代的整个发育过程中至少部分地在父本着丝粒上传递。我们得出结论，果蝇精子中预先存在的CenH3因此不仅是跨代着丝粒维持所必需的，而且还对这一过程进行数量调控。
Analysis of centromeres in progeny of Drosophila sperm with experimentally altered centromere-specific histone CenH3 levels reveals quantitative inheritance of this epigenetic mark. In Drosophila melanogaster, as in many animal and plant species, centromere identity is specified epigenetically. In proliferating cells, a centromere-specific histone H3 variant (CenH3), named Cid in Drosophila and Cenp-A in humans, is a crucial component of the epigenetic centromere mark. Hence, maintenance of the amount and chromosomal location of CenH3 during mitotic proliferation is important. Interestingly, CenH3 may have different roles during meiosis and the onset of embryogenesis. In gametes of Caenorhabditis elegans, and possibly in plants, centromere marking is independent of CenH3. Moreover, male gamete differentiation in animals often includes global nucleosome for protamine exchange that potentially could remove CenH3 nucleosomes. Here we demonstrate that the control of Cid loading during male meiosis is distinct from the regulation observed during the mitotic cycles of early embryogenesis. But Cid is present in mature sperm. After strong Cid depletion in sperm, paternal centromeres fail to integrate into the gonomeric spindle of the first mitosis, resulting in gynogenetic haploid embryos. Furthermore, after moderate depletion, paternal centromeres are unable to re-acquire normal Cid levels in the next generation. We conclude that Cid in sperm is an essential component of the epigenetic centromere mark on paternal chromosomes and it exerts quantitative control over centromeric Cid levels throughout development. Hence, the amount of Cid that is loaded during each cell cycle appears to be determined primarily by the preexisting centromeric Cid, with little flexibility for compensation of accidental losses. Genetic information in eukaryotic cells is parceled into chromosomes. These information strings are precisely transmitted to daughter cells during mitotic and meiotic cell divisions, but only if the centromere, a specialized chromosomal region, is functional. The centromere region within chromosomes of many species—including humans and the fly Drosophila melanogaster—is thought to be specified epigenetically by incorporation of a centromere-specific histone H3 variant (CenH3). After chromosome replication, the centromeres in the resulting two sister chromatids might be expected to be composed of a mixture of pre-existing CenH3 evenly distributed onto the two copies during replication and new CenH3 recruited by the partitioned pool in a stoichiometric manner. Here, we have addressed whether centromeres are indeed replicated in this manner by experimentally altering the levels of centromeric CenH3 in Drosophila sperm. We show that centromeres on paternal chromosomes cannot recruit new CenH3 in embryos fertilized with sperm lacking CenH3. By using sperm with increased or reduced amounts of centromeric CenH3, we demonstrate that altered CenH3 levels are at least partially propagated on paternal centromeres throughout development of the offspring. We conclude that pre-existing CenH3 in Drosophila sperm is therefore not only required for transgenerational centromere maintenance, but that it also exerts quantitative control of this process.
登录
查看更多内容
影响因子：
37.3
作者：
Amato A;Schillaci T;Lentini L;Di Leonardo A
通讯作者：
Di Leonardo A
影响因子：
10.5
作者：
Heeger, S;Leismann, O;Lehner, CF
通讯作者：
Lehner, CF
影响因子：
4.5
作者：
Blower MD;Daigle T;Kaufman T;Karpen GH
通讯作者：
Karpen GH
影响因子：
9.2
作者：
Burrack, Laura S.;Applen, Shelly E.;Berman, Judith
通讯作者：
Berman, Judith
影响因子：
64.5
作者：
Black BE;Cleveland DW
通讯作者：
Cleveland DW