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Phase-separated nuclear bodies of nucleoporin fusions promote condensation of MLL1/CRM1 and rearrangement of 3D genome structure
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Oka, Masahiro, Otani, Mayumi, Miyamoto, Yoichi, Oshima, Rieko, Adachi, Jun, Tomonaga, Takeshi, Asally, Munehiro, Nagaoka, Yuya, Tanaka, Kaori, Toyoda, Atsushi, Ichikawa, Kazuki, Morishita, Shinichi, Isono, Kyoichi, Koseki, Haruhiko, Nakato, Ryuichiro, Ohkawa, Yasuyuki and Yoneda, Yoshihiro (2023) Phase-separated nuclear bodies of nucleoporin fusions promote condensation of MLL1/CRM1 and rearrangement of 3D genome structure. Cell Reports, 42 (8). 112884. doi:10.1016/j.celrep.2023.112884 ISSN 2211-1247.
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Official URL: http://doi.org/10.1016/j.celrep.2023.112884
Abstract
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.
Item Type: | Journal Article | ||||||||||||||||||||||||||||||||||||
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Subjects: | Q Science > QH Natural history > QH426 Genetics | ||||||||||||||||||||||||||||||||||||
Divisions: | Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) | ||||||||||||||||||||||||||||||||||||
Library of Congress Subject Headings (LCSH): | Gene fusion, Leukemia, Homeobox genes, Molecular biology, Cancer cells, Genomes, Three-dimensional imaging | ||||||||||||||||||||||||||||||||||||
Journal or Publication Title: | Cell Reports | ||||||||||||||||||||||||||||||||||||
Publisher: | Elsevier Inc. | ||||||||||||||||||||||||||||||||||||
ISSN: | 2211-1247 | ||||||||||||||||||||||||||||||||||||
Official Date: | 29 August 2023 | ||||||||||||||||||||||||||||||||||||
Dates: |
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Volume: | 42 | ||||||||||||||||||||||||||||||||||||
Number: | 8 | ||||||||||||||||||||||||||||||||||||
Article Number: | 112884 | ||||||||||||||||||||||||||||||||||||
DOI: | 10.1016/j.celrep.2023.112884 | ||||||||||||||||||||||||||||||||||||
Status: | Peer Reviewed | ||||||||||||||||||||||||||||||||||||
Publication Status: | Published | ||||||||||||||||||||||||||||||||||||
Access rights to Published version: | Open Access (Creative Commons) | ||||||||||||||||||||||||||||||||||||
Copyright Holders: | © 2023 The Authors. | ||||||||||||||||||||||||||||||||||||
Date of first compliant deposit: | 9 August 2023 | ||||||||||||||||||||||||||||||||||||
Date of first compliant Open Access: | 9 August 2023 | ||||||||||||||||||||||||||||||||||||
RIOXX Funder/Project Grant: |
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