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多能性因子与高阶染色质组织之间的相互作用。

Crosstalk between pluripotency factors and higher-order chromatin organization.

作者信息

Lopes Novo Clara, Rugg-Gunn Peter

机构信息

a Epigenetics Program , Babraham Institute , Cambridge , UK.

出版信息

Nucleus. 2016 Sep 2;7(5):447-452. doi: 10.1080/19491034.2016.1248013.

DOI:10.1080/19491034.2016.1248013
PMID:27759487
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5120593/
Abstract

Pluripotent cells are characterized by a globally open and accessible chromatin organization that is thought to contribute to cellular plasticity and developmental decision-making. We recently identified the pluripotency factor Nanog as a key regulator of this form of chromatin architecture in mouse embryonic stem cells. In particular, we demonstrated that the transcription factors Nanog and Sall1 co-dependently mediate the epigenetic state of pericentromeric heterochromatin to reinforce a more open and accessible organization in pluripotent cells. Here, we summarize our main findings and place the work into a broader context. We explore how heterochromatin domains could be targets of transcriptional networks in pluripotent cells and are coordinated with cell state. We propose this integration may be to balance the requirement for a dynamic and plastic chromatin organization in pluripotent cells, together with priming for a more restrictive nuclear compartmentalization that is triggered rapidly upon lineage commitment.

摘要

多能细胞的特征在于其全局开放且易于接近的染色质组织,这种组织被认为有助于细胞可塑性和发育决策。我们最近确定多能性因子Nanog是小鼠胚胎干细胞中这种染色质结构形式的关键调节因子。特别是,我们证明转录因子Nanog和Sall1共同依赖地介导着丝粒周围异染色质的表观遗传状态,以加强多能细胞中更开放且易于接近的组织。在这里,我们总结了我们的主要发现,并将这项工作置于更广泛的背景中。我们探讨了异染色质结构域如何成为多能细胞中转录网络的靶点,并与细胞状态相协调。我们提出这种整合可能是为了平衡多能细胞中对动态和可塑性染色质组织的需求,同时为在谱系定向时迅速触发的更具限制性的核区室化做好准备。

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本文引用的文献

1
The pluripotency factor Nanog regulates pericentromeric heterochromatin organization in mouse embryonic stem cells.多能性因子Nanog调节小鼠胚胎干细胞中的着丝粒周围异染色质组织。
Genes Dev. 2016 May 1;30(9):1101-15. doi: 10.1101/gad.275685.115. Epub 2016 Apr 28.
2
Building up the nucleus: nuclear organization in the establishment of totipotency and pluripotency during mammalian development.构建细胞核:哺乳动物发育过程中全能性和多能性建立过程中的核组织
Genes Dev. 2016 Mar 15;30(6):611-21. doi: 10.1101/gad.273805.115.
3
Characterization and dynamics of pericentromere-associated domains in mice.
Front Genet. 2018 Dec 21;9:674. doi: 10.3389/fgene.2018.00674. eCollection 2018.
小鼠中着丝粒周围相关结构域的特征与动态变化
Genome Res. 2015 Jul;25(7):958-69. doi: 10.1101/gr.186643.114. Epub 2015 Apr 16.
4
Embryonic stem cell specific "master" replication origins at the heart of the loss of pluripotency.胚胎干细胞特异性“主”复制起点是多能性丧失的核心。
PLoS Comput Biol. 2015 Feb 6;11(2):e1003969. doi: 10.1371/journal.pcbi.1003969. eCollection 2015 Feb.
5
lncRNA maturation to initiate heterochromatin formation in the nucleolus is required for exit from pluripotency in ESCs.lncRNA 的成熟启动了核仁中异染色质的形成,这对于 ESC 从多能性中退出是必需的。
Cell Stem Cell. 2014 Dec 4;15(6):720-34. doi: 10.1016/j.stem.2014.10.005.
6
The pluripotent genome in three dimensions is shaped around pluripotency factors.多能性基因组在三维空间中围绕多能性因子形成。
Nature. 2013 Sep 12;501(7466):227-31. doi: 10.1038/nature12420. Epub 2013 Jul 24.
7
Something silent this way forms: the functional organization of the repressive nuclear compartment.以这种静默的方式形成了:抑制性核区室的功能组织。
Annu Rev Cell Dev Biol. 2013;29:241-70. doi: 10.1146/annurev-cellbio-101512-122317. Epub 2013 Jul 5.
8
Functional implications of genome topology.基因组拓扑结构的功能意义。
Nat Struct Mol Biol. 2013 Mar;20(3):290-9. doi: 10.1038/nsmb.2474.
9
Chromatin decondensation and nuclear softening accompany Nanog downregulation in embryonic stem cells.染色质解凝聚和核软化伴随着胚胎干细胞中 Nanog 的下调。
Biophys J. 2012 Nov 21;103(10):2060-70. doi: 10.1016/j.bpj.2012.10.015. Epub 2012 Nov 20.
10
A transcription factor-based mechanism for mouse heterochromatin formation.基于转录因子的小鼠异染色质形成机制。
Nat Struct Mol Biol. 2012 Oct;19(10):1023-30. doi: 10.1038/nsmb.2382. Epub 2012 Sep 16.