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Expression and epigenomic landscape of the sex chromosomes in mouse post-meiotic male germ cells

机译：小鼠减数分裂后雄性生殖细胞中性染色体的表达及表观基因组学情况

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Background During meiosis, the X and Y chromosomes are transcriptionally silenced. The persistence of repressive chromatin marks on the sex chromatin after meiosis initially led to the assumption that XY gene silencing persists to some extent in spermatids. Considering the many reports of XY-linked genes expressed and needed in the post-meiotic phase of mouse spermatogenesis, it is still unclear whether or not the mouse sex chromatin is a repressive or permissive environment, after meiosis. Results To determine the transcriptional and chromatin state of the sex chromosomes after meiosis, we re-analyzed ten ChIP-Seq datasets performed on mouse round spermatids and four RNA-seq datasets from male germ cells purified at different stages of spermatogenesis. For this, we used the last version of the genome (mm10/GRCm38) and included reads that map to several genomic locations in order to properly interpret the high proportion of sex chromosome-encoded multicopy genes. Our study shows that coverage of active epigenetic marks H3K4me3 and Kcr is similar on the sex chromosomes and on autosomes. The post-meiotic sex chromatin nevertheless differs from autosomal chromatin in its enrichment in H3K9me3 and its depletion in H3K27me3 and H4 acetylation. We also identified a posttranslational modification, H3K27ac, which specifically accumulates on the Y chromosome. In parallel, we found that the X and Y chromosomes are enriched in genes expressed post-meiotically and display a higher proportion of spermatid-specific genes compared to autosomes. Finally, we observed that portions of chromosome 14 and of the sex chromosomes share specific features, such as enrichment in H3K9me3 and the presence of multicopy genes that are specifically expressed in round spermatids, suggesting that parts of chromosome 14 are under the same evolutionary constraints than the sex chromosomes. Conclusions Based on our expression and epigenomic studies, we conclude that, after meiosis, the mouse sex chromosomes are no longer silenced but are nevertheless regulated differently than autosomes and accumulate different chromatin marks. We propose that post-meiotic selective constraints are at the basis of the enrichment of spermatid-specific genes and of the peculiar chromatin composition of the sex chromosomes and of parts of chromosome 14.
机译：背景在减数分裂期间，X和Y染色体在转录上被沉默。减数分裂后性染色质上抑制性染色质标记的持久性最初导致了这样一个假设，即在精子中XY基因沉默在某种程度上持续存在。考虑到在小鼠精子发生后减数分裂阶段表达和需要的XY连锁基因的许多报道，尚不清楚减数分裂后小鼠性染色质是抑制性还是允许性环境。结果为了确定减数分裂后性染色体的转录和染色质状态，我们重新分析了在小鼠圆形精子上进行的十个ChIP-Seq数据集和在精子形成不同阶段纯化的雄性生殖细胞的四个RNA-seq数据集。为此，我们使用了基因组的最新版本（mm10 / GRCm38），并包含了映射到多个基因组位置的读段，以便正确解释高比例的性染色体编码的多拷贝基因。我们的研究表明，在性染色体和常染色体上，活性表观遗传标记H3K4me3和Kcr的覆盖范围相似。然而，减数分裂后的性染色质与常染色体染色质的不同之处在于其富含H3K9me3以及其耗尽了H3K27me3和H4乙酰化。我们还确定了翻译后修饰H3K27ac，该修饰专门积聚在Y染色体上。同时，我们发现X和Y染色体富含减数分裂后表达的基因，并且显示出比常染色体更高的精子特异性基因比例。最后，我们观察到第14号染色体和性染色体的某些部分具有特定的特征，例如H3K9me3的富集和在圆形精子细胞中特异性表达的多拷贝基因的存在，这表明第14号染色体的部分受相同的进化限制。性染色体。结论根据我们的表达和表观基因组研究，我们得出结论，减数分裂后，小鼠性染色体不再沉默，但与常染色体的调控不同，并积累了不同的染色质标记。我们提出减数分裂后的选择性限制是精子特异性基因的丰富以及性染色体和部分14号染色体的独特染色质组成的基础。

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