Doynova Malina D, Markworth James F, Cameron-Smith David, Vickers Mark H, O'Sullivan Justin M
Liggins Insitute, University of Auckland, Grafton, Auckland, 1032, New Zealand.
Liggins Institute, University of Auckland, Private Bag 92019, Auckland, 1142, New Zealand.
Skelet Muscle. 2017 Apr 5;7(1):5. doi: 10.1186/s13395-017-0122-1.
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.
真核生物基因组的空间组织促进并反映了细胞中正在发生的潜在核过程。因此，基因组的空间组织代表了基因组生物学的一个窗口，通过它能够分析有助于哺乳动物发育的核调控过程。
在本研究中，利用Hi-C和RNA测序技术，在存在或不存在胞苷类似物阿糖胞苷（AraC）的情况下，捕获小鼠肌肉祖细胞（C2C12成肌细胞）分化为肌管前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，但我们观察到了显著的局部和全局发育变化。值得注意的是，在不同发育阶段转录水平变化最大的基因主要位于常染色质区室。HIST1基因座内依赖复制的组蛋白变体的表达发生了显著的重组和变化。最后，用AraC处理终末分化的肌管导致了一组均参与细胞焦亡的基因的转录组和三维基因组组织的额外变化。
总体而言，我们的结果为通过染色质结构机制介导的肌肉细胞对发育和环境刺激的特异性反应提供了证据。
Zotero 插件
