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经典Wnt信号通路在骨骼肌终末分化过程中调节Setdb1的核输出。

Canonical Wnt signalling regulates nuclear export of Setdb1 during skeletal muscle terminal differentiation.

作者信息

Beyer Sophie, Pontis Julien, Schirwis Elija, Battisti Valentine, Rudolf Anja, Le Grand Fabien, Ait-Si-Ali Slimane

机构信息

Centre National de la Recherche Scientifique CNRS-Université Paris Diderot, Sorbonne Paris Cité, Epigenetics and Cell Fate UMR7216 , Paris, France.

Institut Cochin, Université Paris-Descartes, Centre National de la Recherche Scientifique (CNRS) UMR8104, Paris, France; Institut National de la Santé et de la Recherche Médicale (INSERM) U1016, Paris, France.

出版信息

Cell Discov. 2016 Oct 18;2:16037. doi: 10.1038/celldisc.2016.37. eCollection 2016.

DOI:10.1038/celldisc.2016.37
PMID:27790377
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5067623/
Abstract

The histone 3 lysine 9 methyltransferase Setdb1 is essential for both stem cell pluripotency and terminal differentiation of different cell types. To shed light on the roles of Setdb1 in these mutually exclusive processes, we used mouse skeletal myoblasts as a model of terminal differentiation. studies on isolated single myofibres showed that Setdb1 is required for adult muscle stem cells expansion following activation. studies in skeletal myoblasts confirmed that Setdb1 suppresses terminal differentiation. Genomic binding analyses showed a release of Setdb1 from selected target genes upon myoblast terminal differentiation, concomitant to a nuclear export of Setdb1 to the cytoplasm. Both genomic release and cytoplasmic Setdb1 relocalisation during differentiation were dependent on canonical Wnt signalling. Transcriptomic assays in myoblasts unravelled a significant overlap between Setdb1 and Wnt3a regulated genetic programmes. Together, our findings revealed Wnt-dependent subcellular relocalisation of Setdb1 as a novel mechanism regulating Setdb1 functions and myogenesis.

摘要

组蛋白3赖氨酸9甲基转移酶Setdb1对于干细胞多能性和不同细胞类型的终末分化都至关重要。为了阐明Setdb1在这些相互排斥的过程中的作用,我们使用小鼠骨骼肌成肌细胞作为终末分化的模型。对分离出的单个肌纤维的研究表明,Setdb1是成年肌肉干细胞激活后增殖所必需的。对骨骼肌成肌细胞的研究证实,Setdb1抑制终末分化。基因组结合分析表明,成肌细胞终末分化时,Setdb1从选定的靶基因上释放,同时Setdb1向细胞质进行核输出。分化过程中的基因组释放和细胞质Setdb1重新定位均依赖于经典Wnt信号通路。对成肌细胞的转录组分析揭示了Setdb1和Wnt3a调控的遗传程序之间存在显著重叠。总之,我们的研究结果揭示了Setdb1依赖Wnt的亚细胞重新定位是一种调节Setdb1功能和肌生成的新机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d69a/5067623/75d7574dc037/celldisc201637-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d69a/5067623/3f97ae44bd8f/celldisc201637-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d69a/5067623/ba02ff3eaba4/celldisc201637-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d69a/5067623/890870c3caa1/celldisc201637-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d69a/5067623/0e5c01b23682/celldisc201637-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d69a/5067623/0163b5099672/celldisc201637-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d69a/5067623/75d7574dc037/celldisc201637-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d69a/5067623/3f97ae44bd8f/celldisc201637-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d69a/5067623/ba02ff3eaba4/celldisc201637-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d69a/5067623/890870c3caa1/celldisc201637-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d69a/5067623/0e5c01b23682/celldisc201637-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d69a/5067623/0163b5099672/celldisc201637-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d69a/5067623/75d7574dc037/celldisc201637-f6.jpg

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Biochem Biophys Res Commun. 2015 Oct 2;465(4):725-31. doi: 10.1016/j.bbrc.2015.08.065. Epub 2015 Aug 18.
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SETDB1 modulates PRC2 activity at developmental genes independently of H3K9 trimethylation in mouse ES cells.
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