LOXL2-mediated chromatin compaction is required to maintain the oncogenic properties of triple-negative breast cancer cells.
H2A.Z
LOXL2
breast cancer
heterochromatin
oxidation
Journal
The FEBS journal
ISSN: 1742-4658
Titre abrégé: FEBS J
Pays: England
ID NLM: 101229646
Informations de publication
Date de publication:
07 Mar 2024
07 Mar 2024
Historique:
revised:
02
01
2024
received:
01
06
2023
accepted:
23
02
2024
medline:
7
3
2024
pubmed:
7
3
2024
entrez:
7
3
2024
Statut:
aheadofprint
Résumé
Oxidation of histone H3 at lysine 4 (H3K4ox) is catalyzed by lysyl oxidase homolog 2 (LOXL2). This histone modification is enriched in heterochromatin in triple-negative breast cancer (TNBC) cells and has been linked to the maintenance of compacted chromatin. However, the molecular mechanism underlying this maintenance is still unknown. Here, we show that LOXL2 interacts with RuvB-Like 1 (RUVBL1), RuvB-Like 2 (RUVBL2), Actin-like protein 6A (ACTL6A), and DNA methyltransferase 1associated protein 1 (DMAP1), a complex involved in the incorporation of the histone variant H2A.Z. Our experiments indicate that this interaction and the active form of RUVBL2 are required to maintain LOXL2-dependent chromatin compaction. Genome-wide experiments showed that H2A.Z, RUVBL2, and H3K4ox colocalize in heterochromatin regions. In the absence of LOXL2 or RUVBL2, global levels of the heterochromatin histone mark H3K9me3 were strongly reduced, and the ATAC-seq signal in the H3K9me3 regions was increased. Finally, we observed that the interplay between these series of events is required to maintain H3K4ox-enriched heterochromatin regions, which in turn is key for maintaining the oncogenic properties of the TNBC cell line tested (MDA-MB-231).
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Salud Carlos III (ISCIII) FIS/FEDER
ID : PI12/01250
Organisme : Salud Carlos III (ISCIII) FIS/FEDER
ID : CP08/00223
Organisme : Salud Carlos III (ISCIII) FIS/FEDER
ID : PI16/00253
Organisme : Salud Carlos III (ISCIII) FIS/FEDER
ID : CB16/12/00449
Organisme : Ministerio de Economía y Competitividad
ID : FPU14/04071
Organisme : MINECO
ID : IJCI-2014-20723
Organisme : MICIU
ID : PGC2018-095616-B-I00/GINDATA
Organisme : Breast Cancer Research Foundation
ID : BCRF-17-008
Organisme : ISCIII, Red Temática de Investigación Cooperativa en Cáncer
ID : RD012/0036/005
Organisme : EMBO
Organisme : CIHR
Organisme : ISCIII
ID : PT17/0019
Organisme : ERDF
Organisme : Fundación Fero
Organisme : Fundació La Caixa
ID : LCF/PR/PR12/51070001
Informations de copyright
© 2024 Federation of European Biochemical Societies.
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