Random replication of the inactive X chromosome.

Random replication of the inactive X chromosome.
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DOI:
10.1101/gr.161828.113
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发表时间:
2014-01
期刊:
影响因子:
7
通讯作者:
McCarroll SA
McCarroll SA
中科院分区:
生物学1区
文献类型:
--
作者:
Koren A;McCarroll SA

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在真核细胞中,基因组DNA按一定的时间顺序复制。非活性X染色体(Xi)是哺乳动物中最广泛的同时性异染色质,其复制晚于活性X染色体(Xa),但非活性染色质的复制动力学尚不清楚。通过以等位基因特异性、染色体分期的方式分析人类DNA复制,我们首次分别确定了沿活性和非活性染色体(Xa和Xi)的复制时间。Xi的复制不同于Xa的复制,在个体之间有所不同,类似于一个随机的、非结构化的过程。Xi复制迅速,在很大程度上与常染色质基因组分离。复制后期,常染色体上转录不活跃的区域也以非结构化的方式复制,类似于Xi。我们得出结论,DNA复制遵循两种策略:与转录活性相关的缓慢有序复制和沉默染色质的快速随机复制。这两种策略在同一细胞中共存,但在空间和时间上是隔离的。
In eukaryotic cells, genomic DNA replicates in a defined temporal order. The inactive X chromosome (Xi), the most extensive instance of facultative heterochromatin in mammals, replicates later than the active X chromosome (Xa), but the replication dynamics of inactive chromatin are not known. By profiling human DNA replication in an allele-specific, chromosomally phased manner, we determined for the first time the replication timing along the active and inactive chromosomes (Xa and Xi) separately. Replication of the Xi was different from that of the Xa, varied among individuals, and resembled a random, unstructured process. The Xi replicated rapidly and at a time largely separable from that of the euchromatic genome. Late-replicating, transcriptionally inactive regions on the autosomes also replicated in an unstructured manner, similar to the Xi. We conclude that DNA replication follows two strategies: slow, ordered replication associated with transcriptional activity, and rapid, random replication of silent chromatin. The two strategies coexist in the same cell, yet are segregated in space and time.
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