TULIPs decorate the three-dimensional genome of PFA ependymoma

IF 45.5 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Cell Pub Date : 2024-07-09 DOI:10.1016/j.cell.2024.06.023

Michael J. Johnston, John J.Y. Lee, Bo Hu, Ana Nikolic, Elham Hasheminasabgorji, Audrey Baguette, Seungil Paik, Haifen Chen, Sachin Kumar, Carol C.L. Chen, Selin Jessa, Polina Balin, Vernon Fong, Melissa Zwaig, Kulandaimanuvel Antony Michealraj, Xun Chen, Yanlin Zhang, Srinidhi Varadharajan, Pierre Billon, Nikoleta Juretic, Marco Gallo

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Abstract

Posterior fossa group A (PFA) ependymoma is a lethal brain cancer diagnosed in infants and young children. The lack of driver events in the PFA linear genome led us to search its 3D genome for characteristic features. Here, we reconstructed 3D genomes from diverse childhood tumor types and uncovered a global topology in PFA that is highly reminiscent of stem and progenitor cells in a variety of human tissues. A remarkable feature exclusively present in PFA are type B ultra long-range interactions in PFAs (TULIPs), regions separated by great distances along the linear genome that interact with each other in the 3D nuclear space with surprising strength. TULIPs occur in all PFA samples and recur at predictable genomic coordinates, and their formation is induced by expression of EZHIP. The universality of TULIPs across PFA samples suggests a conservation of molecular principles that could be exploited therapeutically.

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TULIPs 装饰了 PFA 上皮瘤的三维基因组

后窝 A 组（PFA）外胚瘤是一种致命的脑癌，多见于婴幼儿。PFA线性基因组中缺乏驱动事件，这促使我们寻找其三维基因组的特征。在这里，我们重建了来自不同儿童肿瘤类型的三维基因组，发现了PFA的全局拓扑结构，它与多种人体组织中的干细胞和祖细胞高度相似。PFA中独有的一个显著特点是PFA中的B型超远距离相互作用（TULIPs），这些区域沿着线性基因组相隔很远，但在三维核空间中却以惊人的强度相互影响。TULIPs 出现在所有 PFA 样本中，并在可预测的基因组坐标上重复出现，其形成是由 EZHIP 的表达诱导的。TULIPs 在 PFA 样本中的普遍性表明，其分子原理是一致的，可以在治疗上加以利用。

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来源期刊

Cell 生物-生化与分子生物学

CiteScore

110.00

自引率

0.80%

发文量

396

审稿时长

2 months

期刊介绍： Cells is an international, peer-reviewed, open access journal that focuses on cell biology, molecular biology, and biophysics. It is affiliated with several societies, including the Spanish Society for Biochemistry and Molecular Biology (SEBBM), Nordic Autophagy Society (NAS), Spanish Society of Hematology and Hemotherapy (SEHH), and Society for Regenerative Medicine (Russian Federation) (RPO). The journal publishes research findings of significant importance in various areas of experimental biology, such as cell biology, molecular biology, neuroscience, immunology, virology, microbiology, cancer, human genetics, systems biology, signaling, and disease mechanisms and therapeutics. The primary criterion for considering papers is whether the results contribute to significant conceptual advances or raise thought-provoking questions and hypotheses related to interesting and important biological inquiries. In addition to primary research articles presented in four formats, Cells also features review and opinion articles in its "leading edge" section, discussing recent research advancements and topics of interest to its wide readership.

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