Reorganized 3D Genome Structures Support Transcriptional Regulation in Mouse Spermatogenesis
Reorganized 3D Genome Structures Support Transcriptional Regulation in Mouse Spermatogenesis
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重组的 3D 基因组结构支持小鼠精子发生的转录调控
DOI：
10.1016/j.isci.2020.101034
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发表时间：
2020-04-24
期刊：
影响因子：
5.8
通讯作者：
Song, Xiaoyuan
中科院分区：
文献类型：
--
作者：
Luo, Zhengyu;Wang, Xiaorong;Song, Xiaoyuan
三维染色质结构在哺乳动物精子发生过程中经历动态重组，然而，它们对基因调控的影响仍不清楚。本研究利用Hi-C等组学技术对小鼠精子发生5个阶段减数分裂染色体的结构与功能调控进行了研究。除了证实最近的报告中关于分区和重组的拓扑相关结构域（TADs）的变化，我们进一步证明，染色质环存在之前和之后，但不是在粗线期阶段。通过整合Hi-C和RNA-seq数据，我们发现生精阶段之间A/B区室的转换与减数分裂特异性mRNA和piRNA表达密切相关。此外，我们的ATAC-seq数据表明，染色质可及性本身并不负责粗线期的环和环减少。此外，我们的ChIP-seq数据表明，CTCF和粘着蛋白在整个减数分裂过程中保持结合在细胞边界区域，这表明TADs的动态重组不需要CTCF和粘着蛋白清除。
Three-dimensional chromatin structures undergo dynamic reorganization during mammalian spermatogenesis; however, their impacts on gene regulation remain unclear. Here, we focused on understanding the structure-function regulation of meiotic chromosomes by Hi-C and other omics techniques in mouse spermatogenesis across five stages. Beyond confirming recent reports regarding changes in compartmentalization and reorganization of topologically associating domains (TADs), we further demonstrated that chromatin loops are present prior to and after, but not at, the pachytene stage. By integrating Hi-C and RNA-seq data, we showed that the switching of A/B compartments between spermatogenic stages is tightly associated with meiosis-specific mRNAs and piRNAs expression. Moreover, our ATAC-seq data indicated that chromatin accessibility per se is not responsible for the TAD and loop diminishment at pachytene. Additionally, our ChIP-seq data demonstrated that CTCF and cohesin remain bound at TAD boundary regions throughout meiosis, suggesting that dynamic reorganization of TADs does not require CTCF and cohesin clearance.