Epigenetic analyses of the planarian genome reveals conservation of bivalent promoters in animal stem cells.
Epigenetic analyses of the planarian genome reveals conservation of bivalent promoters in animal stem cells.
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涡虫基因组的表观遗传学分析揭示了动物干细胞中二价启动子的保守性。
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发表时间：
2017
期刊：
影响因子：
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通讯作者：
A. Aboobaker
中科院分区：
文献类型：
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作者：
Anish Dattani;Damian Kao;Y. Mihaylova;Prasad Abnave;S. Hughes;Alvina G. Lai;Sounak Sahu;A. Aboobaker
Planarian扁形虫具有无限的再生能力，这是由于多能成体干细胞（neoblast）的种群。先前的研究表明，它们具有与多能哺乳动物胚胎干细胞和生殖系干细胞共同的特征。然而，很少有人知道这些细胞的表观遗传调控的重要性，这可能是至关重要的neoblast生物学和再生。我们着手为真涡虫开发分析和实验工具，以研究neoblast中的表观遗传标记，并将该模型系统与其他动物进行直接比较。我们开发了一种针对真涡虫新成细胞的优化ChIP-seq方案，使我们能够生成H3 K4 me 1、H3 K4 me 3和H3 K27 me 3的全基因组图谱。如预期的，发现这些与来自真涡虫RNA-seq数据分析的全基因组表达谱相关。我们发现，许多基因是沉默的neoblasts，然后开关在有丝分裂后的后代在分化过程中有H3 K4 me 3和H3 K27 me 3在启动子区，因此是二价的。进一步的分析表明，二价存在于多能新生细胞群体中的数百个位点。我们证实，表观遗传调控是关键的neoblast生物学和双价启动子不限于脊椎动物谱系，但可能是一个保守的功能，动物干细胞。我们的工作进一步建立了涡虫neoblast作为一个强大的模型系统，了解多能性和再生的表观遗传调控
Planarian flatworms have an indefinite capacity to regenerate due to a population of pluripotent adult stem cells (neoblasts). Previous studies have suggested that they have features in common with both pluripotent mammalian embryonic stem cells and germ line stem cells. However, little is known about the importance of epigenetic regulation in these cells, which is likely to be crucial for neoblast biology and regeneration. We set out to develop analytical and experimental tools for planarians to allow the study of epigenetic marks in neoblasts and allow direct comparison of this model system with other animals. We developed an optimized ChIP-seq protocol for planarian neoblasts that allowed us to generate genome wide profiles for H3K4me1, H3K4me3 and H3K27me3. These were found to correlate as expected with genome wide expression profiles from analyses of planarian RNA-seq data. We found that many genes that are silent in neoblasts and then switch in post-mitotic progeny during differentiation have both H3K4me3 and H3K27me3 at promoter regions and are therefore bivalent. Further analysis suggested that bivalency is present at hundreds of loci in the pluripotent neoblast population. We confirm that epigenetic regulation is key to neoblast biology and that bivalent promoters are not confined to vertebrate lineages, but may be a conserved feature of animal stem cells. Our work further establishes planarian neoblasts as a powerful model system for understanding the epigenetic regulation of pluripotency and regeneration
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