Epigenetic analyses of planarian stem cells demonstrate conservation of bivalent histone modifications in animal stem cells.
Epigenetic analyses of planarian stem cells demonstrate conservation of bivalent histone modifications in animal stem cells.
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DOI：
10.1101/gr.239848.118
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发表时间：
2018-10
期刊：
影响因子：
7
通讯作者：
Aboobaker AA
中科院分区：
文献类型：
--
作者：
Dattani A;Kao D;Mihaylova Y;Abnave P;Hughes S;Lai A;Sahu S;Aboobaker AA
Planarian扁形虫具有无限的能力再生缺失或受损的身体部位，这是由于多能成体干细胞称为neoblasts（NB）。目前，关于NB的表观遗传状态的重要性以及组蛋白修饰如何调节稳态和细胞分化的知之甚少。我们已经开发了一种改进和优化的ChIP-seq方案，用于Schmidtea medialacea中的NB，并生成了活性标记H3 K4 me 3和H3 K36 me 3以及抑制标记H3 K4 me 1和H3 K27 me 3的全基因组图谱。发现这些标记的全基因组谱与NB基因表达谱很好地相关。我们发现在NB区室中具有很少转录活性但在分化期间在有丝分裂后后代中开启的基因是二价的，在启动子区域由H3 K4 me 3和H3 K27 me 3标记。为了进一步支持这一假设，二价基因在启动子近端区域也具有高水平的暂停RNA聚合酶II。总的来说，这项研究证实，表观遗传控制是重要的NB转录程序的维护，使二价启动子作为动物干细胞的保守功能，而不是脊椎动物特异性的创新的情况下。通过建立一个强大的ChIP-seq协议和分析方法，我们进一步促进了涡虫作为一个有前途的模型系统，研究组蛋白修饰介导的干细胞功能和分化的调节。
Planarian flatworms have an indefinite capacity to regenerate missing or damaged body parts owing to a population of pluripotent adult stems cells called neoblasts (NBs). Currently, little is known about the importance of the epigenetic status of NBs and how histone modifications regulate homeostasis and cellular differentiation. We have developed an improved and optimized ChIP-seq protocol for NBs in Schmidtea mediterranea and have generated genome-wide profiles for the active marks H3K4me3 and H3K36me3, and suppressive marks H3K4me1 and H3K27me3. The genome-wide profiles of these marks were found to correlate well with NB gene expression profiles. We found that genes with little transcriptional activity in the NB compartment but which switch on in post-mitotic progeny during differentiation are bivalent, being marked by both H3K4me3 and H3K27me3 at promoter regions. In further support of this hypothesis, bivalent genes also have a high level of paused RNA Polymerase II at the promoter-proximal region. Overall, this study confirms that epigenetic control is important for the maintenance of a NB transcriptional program and makes a case for bivalent promoters as a conserved feature of animal stem cells and not a vertebrate-specific innovation. By establishing a robust ChIP-seq protocol and analysis methodology, we further promote planarians as a promising model system to investigate histone modification–mediated regulation of stem cell function and differentiation.
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影响因子：
23.9
作者：
Brookes, Emily;de Santiago, Ines;Hebenstreit, Daniel;Morris, Kelly J.;Carroll, Tom;Xie, Sheila Q.;Stock, Julie K.;Heidemann, Martin;Eick, Dirk;Nozaki, Naohito;Kimura, Hiroshi;Ragoussis, Jiannis;Teichmann, Sarah A.;Pombo, Ana
通讯作者：
Pombo, Ana
影响因子：
16
作者：
Calo, Eliezer;Wysocka, Joanna
通讯作者：
Wysocka, Joanna
影响因子：
16.8
作者：
Hu D;Garruss AS;Gao X;Morgan MA;Cook M;Smith ER;Shilatifard A
通讯作者：
Shilatifard A
影响因子：
44.1
作者：
Hawkins, R. David;Hon, Gary C.;Ren, Bing
通讯作者：
Ren, Bing
影响因子：
4.6
作者：
Bledau, Anita S.;Schmidt, Kerstin;Anastassiadis, Konstantinos
通讯作者：
Anastassiadis, Konstantinos