Recurrent chromosomal translocations in sarcomas create a megacomplex that mislocalizes NuA4/TIP60 to Polycomb target loci.


Journal

Genes & development
ISSN: 1549-5477
Titre abrégé: Genes Dev
Pays: United States
ID NLM: 8711660

Informations de publication

Date de publication:
01 06 2022
Historique:
received: 31 08 2021
accepted: 31 05 2022
pubmed: 17 6 2022
medline: 19 7 2022
entrez: 16 6 2022
Statut: ppublish

Résumé

Chromosomal translocations frequently promote carcinogenesis by producing gain-of-function fusion proteins. Recent studies have identified highly recurrent chromosomal translocations in patients with endometrial stromal sarcomas (ESSs) and ossifying fibromyxoid tumors (OFMTs), leading to an in-frame fusion of PHF1 (PCL1) to six different subunits of the NuA4/TIP60 complex. While NuA4/TIP60 is a coactivator that acetylates chromatin and loads the H2A.Z histone variant, PHF1 is part of the Polycomb repressive complex 2 (PRC2) linked to transcriptional repression of key developmental genes through methylation of histone H3 on lysine 27. In this study, we characterize the fusion protein produced by the

Identifiants

pubmed: 35710139
pii: gad.348982.121
doi: 10.1101/gad.348982.121
pmc: PMC9296003
doi:

Substances chimiques

Chromatin 0
DNA-Binding Proteins 0
Histones 0
Polycomb-Group Proteins 0
Polycomb Repressive Complex 2 EC 2.1.1.43

Types de publication

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

Langues

eng

Sous-ensembles de citation

IM

Pagination

664-683

Subventions

Organisme : CIHR
ID : FDN-143314
Pays : Canada

Informations de copyright

© 2022 Sudarshan et al.; Published by Cold Spring Harbor Laboratory Press.

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Auteurs

Deepthi Sudarshan (D)

Centre Hospitalier Universitaire (CHU) de Québec-Université Laval Research Center, Laval University Cancer Research Center, Québec City, Québec G1R 3S3, Canada.

Nikita Avvakumov (N)

Centre Hospitalier Universitaire (CHU) de Québec-Université Laval Research Center, Laval University Cancer Research Center, Québec City, Québec G1R 3S3, Canada.

Marie-Eve Lalonde (ME)

Centre Hospitalier Universitaire (CHU) de Québec-Université Laval Research Center, Laval University Cancer Research Center, Québec City, Québec G1R 3S3, Canada.

Nader Alerasool (N)

Donnelly Centre for Cellular and Biomolecular Research, Department of Molecular Genetics, University of Toronto, Toronto, Ontario M5S 3E1, Canada.

Charles Joly-Beauparlant (C)

Computational Biology Laboratory, CHU de Québec-Université Laval Research Center, Québec City, Québec G1V 4G2, Canada.

Karine Jacquet (K)

Centre Hospitalier Universitaire (CHU) de Québec-Université Laval Research Center, Laval University Cancer Research Center, Québec City, Québec G1R 3S3, Canada.

Amel Mameri (A)

Centre Hospitalier Universitaire (CHU) de Québec-Université Laval Research Center, Laval University Cancer Research Center, Québec City, Québec G1R 3S3, Canada.

Jean-Philippe Lambert (JP)

Centre Hospitalier Universitaire (CHU) de Québec-Université Laval Research Center, Laval University Cancer Research Center, Québec City, Québec G1R 3S3, Canada.
Centre for Systems Biology, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario M5G 1X5, Canada.

Justine Rousseau (J)

Institut de Recherches Cliniques de Montréal, Department of Biochemistry and Molecular Medicine, Université de Montréal, Montréal, Québec H3T 1J4, Canada.

Catherine Lachance (C)

Centre Hospitalier Universitaire (CHU) de Québec-Université Laval Research Center, Laval University Cancer Research Center, Québec City, Québec G1R 3S3, Canada.

Eric Paquet (E)

Centre Hospitalier Universitaire (CHU) de Québec-Université Laval Research Center, Laval University Cancer Research Center, Québec City, Québec G1R 3S3, Canada.

Lara Herrmann (L)

Computational Biology Laboratory, CHU de Québec-Université Laval Research Center, Québec City, Québec G1V 4G2, Canada.

Samarth Thonta Setty (S)

Computational Biology Laboratory, CHU de Québec-Université Laval Research Center, Québec City, Québec G1V 4G2, Canada.

Jeremy Loehr (J)

Centre Hospitalier Universitaire (CHU) de Québec-Université Laval Research Center, Laval University Cancer Research Center, Québec City, Québec G1R 3S3, Canada.

Marcus Q Bernardini (MQ)

Department of Gynecologic Oncology, Princess Margaret Cancer Center, University Health Network, Sinai Health System, Toronto, Ontario M5B 2M9, Canada.
Department of Obstetrics and Gynecology, University of Toronto, Toronto, Ontario M5G 1X8, Canada.

Marjan Rouzbahman (M)

Department of Laboratory Medicine and Pathobiology, Princess Margaret Hospital Cancer Centre, Toronto, Ontario M5G 2C4, Canada.

Anne-Claude Gingras (AC)

Centre for Systems Biology, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario M5G 1X5, Canada.

Benoit Coulombe (B)

Institut de Recherches Cliniques de Montréal, Department of Biochemistry and Molecular Medicine, Université de Montréal, Montréal, Québec H3T 1J4, Canada.

Arnaud Droit (A)

Computational Biology Laboratory, CHU de Québec-Université Laval Research Center, Québec City, Québec G1V 4G2, Canada.

Mikko Taipale (M)

Donnelly Centre for Cellular and Biomolecular Research, Department of Molecular Genetics, University of Toronto, Toronto, Ontario M5S 3E1, Canada.

Yannick Doyon (Y)

Centre Hospitalier Universitaire (CHU) de Québec-Université Laval Research Center, Laval University Cancer Research Center, Québec City, Québec G1R 3S3, Canada.

Jacques Côté (J)

Centre Hospitalier Universitaire (CHU) de Québec-Université Laval Research Center, Laval University Cancer Research Center, Québec City, Québec G1R 3S3, Canada.

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