Mammalian X-chromosome dosage balance is regulated by X-chromosome inactivation (XCI) and X-chromosome upregulation (XCU), but the dynamics of XCU as well as the interplay between the two mechanisms remain poorly understood. Here, we mapped XCU throughout early mouse embryonic development at cellular and allelic resolution, revealing sex- and lineage-specific dynamics along key events in X-chromosome regulation. Our data show that XCU is linearly proportional to the degree of XCI, indicating that dosage compensation ensues based on mRNA levels rather than number of active X chromosomes. In line with this, we reveal that the two active X chromosomes in female naive embryonic stem cells are not hyperactive as previously thought. In all lineages, XCU was underlain by increased transcriptional burst frequencies, providing a mechanistic basis in vivo. Together, our results demonstrate unappreciated flexibility of XCU in balancing X-chromosome expression, and we propose a general model for allelic dosage balance, applicable for wider mechanisms of transcriptional regulation.

中文翻译：

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X染色体上调动态链接到X灭活状态

哺乳动物X染色体剂量的平衡是由X染色体失活（XCI）和X染色体上调（XCU）来调节的，但对XCU的动力学以及这两种机制之间的相互作用的了解仍然很少。在这里，我们以细胞和等位基因分辨率在整个小鼠早期胚胎发育过程中绘制了XCU，揭示了沿X染色体调控关键事件的性别和谱系特异性动力学。我们的数据表明XCU与XCI的程度成线性比例，表明剂量补偿是基于mRNA水平而不是基于活跃X染色体的数量进行的。与此相符，我们揭示了女性幼稚胚胎干细胞中的两个活跃的X染色体并不像以前认为的那样活跃。在所有谱系中，XCU都以增加的转录猝发频率为基础，为体内提供了机制基础。