Population variability in X-chromosome inactivation across 9 mammalian species.
Population variability in X-chromosome inactivation across 9 mammalian species.
复制标题
9 种哺乳动物 X 染色体失活的群体变异。
DOI：
10.1101/2023.10.17.562732
复制
发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Gillis,Jesse
中科院分区：
文献类型：
--
作者：
Werner,JonathanM;Hover,John;Gillis,Jesse
雌性哺乳动物的两条X染色体之一在胚胎干细胞中通过X染色体失活而表观遗传沉默。这就产生了一个表达母本或父本X等位基因的细胞镶嵌体。X染色体失活率，即失活的亲本等位基因的比例，在个体之间变化很大，代表了哺乳动物群体中表观遗传变异的最大实例。虽然认识到X染色体失活变异性的各种影响因素，即随机和/或遗传效应，但对其相对贡献知之甚少。这部分是由于有限的跨种属分析，使得难以区分X染色体失活率变异的可推广或种属特异性机制。为了解决这一差距，我们测量X染色体失活率在10个哺乳动物物种（9531个个体样本），从啮齿动物到灵长类动物，并比较随机模型或遗传因素解释X染色体失活变异的强度。我们的研究结果表明，胚胎的X染色体失活的随机性是一个一般的解释模型，在哺乳动物群体X染色体失活的变化，而遗传因素起着次要的作用。
One of the two X-chromosomes in female mammals is epigenetically silenced in embryonic stem cells by X-chromosome inactivation. This creates a mosaic of cells expressing either the maternal or the paternal X allele. The X-chromosome inactivation ratio, the proportion of inactivated parental alleles, varies widely among individuals, representing the largest instance of epigenetic variability within mammalian populations. While various contributing factors to X-chromosome inactivation variability are recognized, namely stochastic and/or genetic effects, their relative contributions are poorly understood. This is due in part to limited cross-species analysis, making it difficult to distinguish between generalizable or species-specific mechanisms for X-chromosome inactivation ratio variability. To address this gap, we measure X-chromosome inactivation ratios in ten mammalian species (9531 individual samples), ranging from rodents to primates, and compare the strength of stochastic models or genetic factors for explaining X-chromosome inactivation variability. Our results demonstrate the embryonic stochasticity of X-chromosome inactivation is a general explanatory model for population X-chromosome inactivation variability in mammals, while genetic factors play a minor role.