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

Humans Nuclear Pore Complex Proteins / metabolism Karyopherins / genetics Homeodomain Proteins / metabolism Leukemia / metabolism Chromatin Receptors, Cytoplasmic and Nuclear / genetics Nuclear Bodies
3D genome CP: Molecular biology CRM1 HOX cluster genes MLL1 NUP214 NUP98 fusion gene leukemia molecular condensation phase separation

Journal

Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691

Informations de publication

Date de publication:
29 08 2023
Historique:
received: 25 01 2023
revised: 29 05 2023
accepted: 13 07 2023
medline: 4 9 2023
pubmed: 30 7 2023
entrez: 30 7 2023
Statut: ppublish

Résumé

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.

Identifiants

DOI: 10.1016/j.celrep.2023.112884 PMID: 37516964
pubmed: 37516964
pii: S2211-1247(23)00895-1
doi: 10.1016/j.celrep.2023.112884
pii:
doi:

Substances chimiques

Nuclear Pore Complex Proteins 0
Karyopherins 0
Homeodomain Proteins 0
Chromatin 0
Receptors, Cytoplasmic and Nuclear 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

112884

Subventions

Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/S506783/1
Pays : United Kingdom

Informations de copyright

Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests The authors declare no competing interests.

Auteurs

Masahiro Oka (M)

Laboratory of Nuclear Transport Dynamics, National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), 7-6-8 Saito-Asagi, Ibaraki, Osaka 567-0085, Japan; Laboratory of Biomedical Innovation, Graduate School of Pharmaceutical Sciences, Osaka University, 1-3 Yamada-oka, Suita, Osaka 565-0871, Japan. Electronic address: moka@nibiohn.go.jp.

Mayumi Otani (M)

Laboratory of Nuclear Transport Dynamics, National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), 7-6-8 Saito-Asagi, Ibaraki, Osaka 567-0085, Japan.

Yoichi Miyamoto (Y)

Laboratory of Nuclear Transport Dynamics, National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), 7-6-8 Saito-Asagi, Ibaraki, Osaka 567-0085, Japan.

Rieko Oshima (R)

Laboratory of Nuclear Transport Dynamics, National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), 7-6-8 Saito-Asagi, Ibaraki, Osaka 567-0085, Japan.

Jun Adachi (J)

Laboratory of Proteomics for Drug Discovery, National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), 7-6-8 Saito-Asagi, Ibaraki, Osaka 567-0085, Japan.

Takeshi Tomonaga (T)

Laboratory of Proteomics for Drug Discovery, National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), 7-6-8 Saito-Asagi, Ibaraki, Osaka 567-0085, Japan.

Munehiro Asally (M)

School of Life Sciences, The University of Warwick, Coventry CV4 7AL, UK.

Yuya Nagaoka (Y)

Institute for Quantitative Biosciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.

Kaori Tanaka (K)

Division of Transcriptomics, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-Ku, Fukuoka 812-8582, Japan.

Atsushi Toyoda (A)

Advanced Genomics Center, National Institute of Genetics, Mishima, Shizuoka 411-8540, Japan.

Kazuki Ichikawa (K)

Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, 5-1-5 Kashiwanoha, Kashiwa, Chiba 277-8568, Japan.

Shinichi Morishita (S)

Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, 5-1-5 Kashiwanoha, Kashiwa, Chiba 277-8568, Japan.

Kyoichi Isono (K)

Laboratory Animal Center, Wakayama Medical University, 811-1 Kimi-idera, Wakayama 641-8509, Japan.

Haruhiko Koseki (H)

Laboratory for Developmental Genetics, RIKEN Center for Integrative Medical Sciences, 1-7-29 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan.

Ryuichiro Nakato (R)

Institute for Quantitative Biosciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan. Electronic address: rnakato@iqb.u-tokyo.ac.jp.

Yasuyuki Ohkawa (Y)

Division of Transcriptomics, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-Ku, Fukuoka 812-8582, Japan. Electronic address: yohkawa@kyushu.in.

Yoshihiro Yoneda (Y)

National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), 7-6-8 Saito-Asagi, Ibaraki, Osaka 567-0085, Japan.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Phase-separated nuclear bodies of nucleoporin...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Protéines de transport membranaire › Transporteurs nucléocytoplasmiques › Complexe protéique du pore nucléaire › Phase-separated nuclear bodies of nucleoporin...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines nucléaires › Caryophérines › Phase-separated nuclear bodies of nucleoporin...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines de liaison à l'ADN › Protéines à homéodomaine › Phase-separated nuclear bodies of nucleoporin...
questionsmedicales.fr › Tumeurs › Tumeurs par type histologique › Leucémies › Phase-separated nuclear bodies of nucleoporin...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Structures de chromosome › Chromatine › Phase-separated nuclear bodies of nucleoporin...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Récepteurs cytoplasmiques et nucléaires › Phase-separated nuclear bodies of nucleoporin...
questionsmedicales.fr › Cellules › Structures cellulaires › Espace intracellulaire › Structures nucléaires › Espace intranucléaire › Corps nucléaires › Phase-separated nuclear bodies of nucleoporin...