TULIPs decorate the three-dimensional genome of PFA ependymoma

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 JureticCraig Daniels, Amulya Nageswara Rao, Caterina Giannini, Eric M. Thompson, Miklos Garami, Peter Hauser, Timea Pocza, Young Shin Ra, Byung Kyu Cho, Seung Ki Kim, Kyu Chang Wang, Ji Yeoun Lee, Wieslawa Grajkowska, Marta Perek-Polnik, Sameer Agnihotri, Stephen Mack, Benjamin Ellezam, Alex Weil, Jeremy Rich, Guillaume Bourque, Jennifer A. Chan, V. Wee Yong, Mathieu Lupien, Jiannis Ragoussis, Claudia Kleinman, Jacek Majewski, Mathieu Blanchette, Nada Jabado, Michael D. Taylor, Marco Gallo

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

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.

Original languageEnglish
JournalCell
DOIs
StateAccepted/In press - 2024

Keywords

  • 3D genome
  • brain tumor
  • childhood cancer
  • chromatin
  • ependymoma
  • epigenomics
  • genomics
  • PFA
  • transcriptomics
  • TULIPs

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