Dynamic reorganization of the genome shapes the recombination landscape in meiotic prophase
Dynamic reorganization of the genome shapes the recombination landscape in meiotic prophase
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DOI：
10.1038/s41594-019-0187-0
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发表时间：
2019-03-01
影响因子：
16.8
通讯作者：
Corbett, Kevin D.
中科院分区：
文献类型：
--
作者：
Patel, Lucas;Kang, Rhea;Corbett, Kevin D.
在减数分裂前期，染色体被组织成紧密的环状阵列，以促进同源配对和重组。在这里，我们用染色体构象捕捉(Hi-C)技术探索了小鼠精母细胞在减数分裂早期和晚期的基因组结构。我们的数据支持所建立的减数分裂染色体环阵列模型，并推断随着染色体紧凑和同源物发生联会，早期平均为0.8-1.0兆碱基对(Mb)的环，晚期前期延伸到1.5-2.0Mb。在减数分裂前期，拓扑相关结构域(TADS)丢失，这表明减数分裂染色体轴的组装改变了染色体相关粘附素复合体的活性。在TADS丢失的同时，在减数分裂前期维持物理上分离的A和B隔室。此外，减数分裂DNA断裂和同源基因间交叉优先形成在基因密集的A区，揭示了染色质组织在减数分裂重组中的作用。最后，对全基因组同源基因间接触的直接检测揭示了同源基因比对和联会复合体并置的结构基础。
In meiotic prophase, chromosomes are organized into compacted loop arrays to promote homolog pairing and recombination. Here, we probe the architecture of the mouse spermatocyte genome in early and late meiotic prophase using chromosome conformation capture (Hi-C). Our data support the established loop array model of meiotic chromosomes, and infer loops averaging 0.8-1.0 megabase pairs (Mb) in early prophase and extending to 1.5-2.0 Mb in late prophase as chromosomes compact and homologs undergo synapsis. Topologically associating domains (TADs) are lost in meiotic prophase, suggesting that assembly of the meiotic chromosome axis alters the activity of chromosome-associated cohesin complexes. While TADs are lost, physically separated A and B compartments are maintained in meiotic prophase. Moreover, meiotic DNA breaks and interhomolog crossovers preferentially form in the gene-dense A compartment, revealing a role for chromatin organization in meiotic recombination. Finally, direct detection of interhomolog contacts genome-wide reveals the structural basis for homolog alignment and juxtaposition by the synaptonemal complex.