Bipartite structure of the inactive mouse X chromosome.
Bipartite structure of the inactive mouse X chromosome.
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DOI：
10.1186/s13059-015-0728-8
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发表时间：
2015-08-07
期刊：
影响因子：
12.3
通讯作者：
Disteche CM
中科院分区：
文献类型：
--
作者：
Deng X;Ma W;Ramani V;Hill A;Yang F;Ay F;Berletch JB;Blau CA;Shendure J;Duan Z;Noble WS;Disteche CM
在哺乳动物中，一条雌性X染色体和所有的印记基因都只从体细胞中的一个等位基因表达。为了评估与等位基因沉默相关的结构变化，我们应用了最近开发的Hi-C检测，该检测使用DNase I对小鼠F1杂交系统进行染色质片段化。我们发现两个雌性小鼠X染色体的构象完全不同。不活跃的X有两个超域的频繁的染色体内的接触分开的边界区域。与最近报道的人类非活性X的两个超结构域结构的比较表明，物种之间的超结构域的基因组内容不同，但部分边界区域是保守的，位于DxZ 4/DXZ 4基因座附近。在小鼠中，边界区也包含一个小卫星，Ds-TR，Dxz 4和Ds-TR似乎都锚定在核仁上。逃避X失活的基因不会聚集，而是位于3D结构的外围附近，CTCF或RNA聚合酶富集的区域也是如此。与活跃等位基因和逃避X失活的基因相比，X失活基因的非活跃等位基因检测到的短距离染色体内接触较少。这种模式对于印记基因也是明显的，其中检测到更多的染色质接触用于表达等位基因。通过应用一种新的Hi-C方法来映射等位基因染色质接触，我们发现了一个特定的二分组织的小鼠不活跃的X染色体，可能在基因沉默的维护中起着重要的作用。本文的在线版本（doi：10.1186/s13059-015-0728-8）包含补充材料，可供授权用户使用。
In mammals, one of the female X chromosomes and all imprinted genes are expressed exclusively from a single allele in somatic cells. To evaluate structural changes associated with allelic silencing, we have applied a recently developed Hi-C assay that uses DNase I for chromatin fragmentation to mouse F1 hybrid systems. We find radically different conformations for the two female mouse X chromosomes. The inactive X has two superdomains of frequent intrachromosomal contacts separated by a boundary region. Comparison with the recently reported two-superdomain structure of the human inactive X shows that the genomic content of the superdomains differs between species, but part of the boundary region is conserved and located near the Dxz4/DXZ4 locus. In mouse, the boundary region also contains a minisatellite, Ds-TR, and both Dxz4 and Ds-TR appear to be anchored to the nucleolus. Genes that escape X inactivation do not cluster but are located near the periphery of the 3D structure, as are regions enriched in CTCF or RNA polymerase. Fewer short-range intrachromosomal contacts are detected for the inactive alleles of genes subject to X inactivation compared with the active alleles and with genes that escape X inactivation. This pattern is also evident for imprinted genes, in which more chromatin contacts are detected for the expressed allele. By applying a novel Hi-C method to map allelic chromatin contacts, we discover a specific bipartite organization of the mouse inactive X chromosome that probably plays an important role in maintenance of gene silencing. The online version of this article (doi:10.1186/s13059-015-0728-8) contains supplementary material, which is available to authorized users.