Cell Reports (Aug 2023)

Phase-separated nuclear bodies of nucleoporin fusions promote condensation of MLL1/CRM1 and rearrangement of 3D genome structure

  • Masahiro Oka,
  • Mayumi Otani,
  • Yoichi Miyamoto,
  • Rieko Oshima,
  • Jun Adachi,
  • Takeshi Tomonaga,
  • Munehiro Asally,
  • Yuya Nagaoka,
  • Kaori Tanaka,
  • Atsushi Toyoda,
  • Kazuki Ichikawa,
  • Shinichi Morishita,
  • Kyoichi Isono,
  • Haruhiko Koseki,
  • Ryuichiro Nakato,
  • Yasuyuki Ohkawa,
  • Yoshihiro Yoneda

Journal volume & issue
Vol. 42, no. 8
p. 112884

Abstract

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Summary: NUP98 and NUP214 form chimeric fusion proteins that assemble into phase-separated nuclear bodies containing CRM1, a nuclear export receptor. However, these nuclear bodies’ function in controlling gene expression remains elusive. Here, we demonstrate that the nuclear bodies of NUP98::HOXA9 and SET::NUP214 promote the condensation of mixed lineage leukemia 1 (MLL1), a histone methyltransferase essential for the maintenance of HOX gene expression. These nuclear bodies are robustly associated with MLL1/CRM1 and co-localized on chromatin. Furthermore, whole-genome chromatin-conformation capture analysis reveals that NUP98::HOXA9 induces a drastic alteration in high-order genome structure at target regions concomitant with the generation of chromatin loops and/or rearrangement of topologically associating domains in a phase-separation-dependent manner. Collectively, these results show that the phase-separated nuclear bodies of nucleoporin fusion proteins can enhance the activation of target genes by promoting the condensation of MLL1/CRM1 and rearrangement of the 3D genome structure.

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