LOXL2-mediated H3K4 oxidation reduces chromatin accessibility in triple-negative breast cancer cells.
Amino Acid Oxidoreductases
/ genetics
Animals
Cell Line, Tumor
Chromatin
/ genetics
DNA Damage
/ genetics
Female
Gene Expression Regulation, Neoplastic
Gene Knockdown Techniques
Heterochromatin
/ genetics
Heterografts
Histone Code
/ genetics
Histones
/ genetics
Humans
Lysine
/ genetics
Mice
Oxidation-Reduction
Triple Negative Breast Neoplasms
/ genetics
Journal
Oncogene
ISSN: 1476-5594
Titre abrégé: Oncogene
Pays: England
ID NLM: 8711562
Informations de publication
Date de publication:
01 2020
01 2020
Historique:
received:
28
01
2019
accepted:
09
08
2019
revised:
08
07
2019
pubmed:
30
8
2019
medline:
21
4
2020
entrez:
30
8
2019
Statut:
ppublish
Résumé
Oxidation of H3 at lysine 4 (H3K4ox) by lysyl oxidase-like 2 (LOXL2) generates an H3 modification with an unknown physiological function. We find that LOXL2 and H3K4ox are higher in triple-negative breast cancer (TNBC) cell lines and patient-derived xenografts (PDXs) than those from other breast cancer subtypes. ChIP-seq revealed that H3K4ox is located primarily in heterochromatin, where it is involved in chromatin compaction. Knocking down LOXL2 reduces H3K4ox levels and causes chromatin decompaction, resulting in a sustained activation of the DNA damage response (DDR) and increased susceptibility to anticancer agents. This critical role that LOXL2 and oxidized H3 play in chromatin compaction and DDR suggests that functionally targeting LOXL2 could be a way to sensitize TNBC cells to conventional therapy.
Identifiants
pubmed: 31462706
doi: 10.1038/s41388-019-0969-1
pii: 10.1038/s41388-019-0969-1
pmc: PMC6937214
doi:
Substances chimiques
Chromatin
0
Heterochromatin
0
Histones
0
Amino Acid Oxidoreductases
EC 1.4.-
LOXL2 protein, human
EC 1.4.3.-
Lysine
K3Z4F929H6
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
79-121Références
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