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端粒外端对端粒的影响:多能性或干性中的新兴分子联系。

Extra-telomeric impact of telomeres: Emerging molecular connections in pluripotency or stemness.

机构信息

Integrative and Functional Biology Unit, CSIR Institute of Genomics and Integrative Biology, New Delhi, India.

Academy of Scientific and Innovative Research (AcSIR), CSIR Institute of Genomics and Integrative Biology, New Delhi, India.

出版信息

J Biol Chem. 2020 Jul 24;295(30):10245-10254. doi: 10.1074/jbc.REV119.009710. Epub 2020 May 22.

Abstract

Telomeres comprise specialized nucleic acid-protein complexes that help protect chromosome ends from DNA damage. Moreover, telomeres associate with subtelomeric regions through looping. This results in altered expression of subtelomeric genes. Recent observations further reveal telomere length-dependent gene regulation and epigenetic modifications at sites spread across the genome and distant from telomeres. This regulation is mediated through the telomere-binding protein telomeric repeat-binding factor 2 (TRF2). These observations suggest a role of telomeres in extra-telomeric functions. Most notably, telomeres have a broad impact on pluripotency and differentiation. For example, cardiomyocytes differentiate with higher efficacy from induced pluripotent stem cells having long telomeres, and differentiated cells obtained from human embryonic stem cells with relatively long telomeres have a longer lifespan. Here, we first highlight reports on these two seemingly distinct research areas: the extra-telomeric role of telomere-binding factors and the role of telomeres in pluripotency/stemness. On the basis of the observations reported in these studies, we draw attention to potential molecular connections between extra-telomeric biology and pluripotency. Finally, in the context of the nonlocal influence of telomeres on pluripotency and stemness, we discuss major opportunities for progress in molecular understanding of aging-related disorders and neurodegenerative diseases.

摘要

端粒由特殊的核酸-蛋白质复合物组成,有助于保护染色体末端免受 DNA 损伤。此外,端粒通过环化与端粒外区域相关联。这导致端粒外基因的表达发生改变。最近的观察进一步揭示了端粒长度依赖性基因调控和基因组上远离端粒的位点的表观遗传修饰。这种调节是通过端粒结合蛋白端粒重复结合因子 2(TRF2)介导的。这些观察表明端粒在端粒外功能中的作用。值得注意的是,端粒对多能性和分化有广泛的影响。例如,具有长端粒的诱导多能干细胞分化为心肌细胞的效率更高,而具有相对长端粒的人胚胎干细胞获得的分化细胞的寿命更长。在这里,我们首先强调了这两个看似截然不同的研究领域的报告:端粒结合因子的端粒外作用以及端粒在多能性/干性中的作用。基于这些研究中报告的观察结果,我们提请注意端粒外生物学和多能性之间潜在的分子联系。最后,在端粒对多能性和干性的非局部影响的背景下,我们讨论了在与衰老相关的疾病和神经退行性疾病的分子理解方面取得进展的主要机会。

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