Linkages between changes in the 3D organization of the genome and transcription during myotube differentiation in vitro.
Linkages between changes in the 3D organization of the genome and transcription during myotube differentiation in vitro.
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DOI：
10.1186/s13395-017-0122-1
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发表时间：
2017-04-05
期刊：
影响因子：
4.9
通讯作者：
O'Sullivan JM
中科院分区：
文献类型：
--
作者：
Doynova MD;Markworth JF;Cameron-Smith D;Vickers MH;O'Sullivan JM
真核生物基因组的空间组织促进并反映了细胞中发生的潜在核过程。因此，基因组的空间组织代表了基因组生物学的一个窗口，可以分析有助于哺乳动物发育的核调控过程。本研究利用Hi-C和RNA-seq技术，在胞苷类似物AraC存在或不存在的情况下，捕捉小鼠肌祖细胞（C2C12成肌细胞）分化为肌管之前和之后的基因组组织和转录组。尽管肌管和成肌细胞基因组之间存在高度相关性，但我们观察到显著的局部和全局发育变化。值得注意的是，在不同发育阶段表现出最大转录水平变化的基因主要在常染色质室内。在HIST1位点内，复制依赖性组蛋白变体的表达发生了显著的重构和变化。最后，用AraC处理终末分化的肌管导致了与焦亡有关的一系列基因的转录组和3D基因组组织的额外变化。总的来说，我们的研究结果为肌肉细胞对发育和环境刺激的特异性反应提供了证据，这些刺激是通过染色质结构机制介导的。本文的在线版本（doi:10.1186/s13395-017-0122-1）包含补充材料，可供授权用户使用。
The spatial organization of eukaryotic genomes facilitates and reflects the underlying nuclear processes that are occurring in the cell. As such, the spatial organization of a genome represents a window on the genome biology that enables analysis of the nuclear regulatory processes that contribute to mammalian development. In this study, Hi-C and RNA-seq were used to capture the genome organization and transcriptome in mouse muscle progenitor cells (C2C12 myoblasts) before and after differentiation to myotubes, in the presence or absence of the cytidine analogue AraC. We observed significant local and global developmental changes despite high levels of correlation between the myotubes and myoblast genomes. Notably, the genes that exhibited the greatest variation in transcript levels between the different developmental stages were predominately within the euchromatic compartment. There was significant re-structuring and changes in the expression of replication-dependent histone variants within the HIST1 locus. Finally, treating terminally differentiated myotubes with AraC resulted in additional changes to the transcriptome and 3D genome organization of sets of genes that were all involved in pyroptosis. Collectively, our results provide evidence for muscle cell-specific responses to developmental and environmental stimuli mediated through a chromatin structure mechanism. The online version of this article (doi:10.1186/s13395-017-0122-1) contains supplementary material, which is available to authorized users.