Super-enhancer-driven expression of BAHCC1 promotes melanoma cell proliferation and genome stability.
BAHCC1
CP: Cancer
gene expression
genome stability
melanoma
super-enhancer
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
28 Nov 2023
28 Nov 2023
Historique:
received:
02
11
2022
revised:
27
07
2023
accepted:
16
10
2023
medline:
4
12
2023
pubmed:
4
11
2023
entrez:
4
11
2023
Statut:
ppublish
Résumé
Super-enhancers (SEs) are stretches of enhancers ensuring a high level of expression of key genes associated with cell function. The identification of cancer-specific SE-driven genes is a powerful means for the development of innovative therapeutic strategies. Here, we identify a MITF/SOX10/TFIIH-dependent SE promoting the expression of BAHCC1 in a broad panel of melanoma cells. BAHCC1 is highly expressed in metastatic melanoma and is required for tumor engraftment, growth, and dissemination. Integrative genomics analyses reveal that BAHCC1 is a transcriptional regulator controlling expression of E2F/KLF-dependent cell-cycle and DNA-repair genes. BAHCC1 associates with BRG1-containing remodeling complexes at the promoters of these genes. BAHCC1 silencing leads to decreased cell proliferation and delayed DNA repair. Consequently, BAHCC1 deficiency cooperates with PARP inhibition to induce melanoma cell death. Our study identifies BAHCC1 as an SE-driven gene expressed in melanoma and demonstrates how its inhibition can be exploited as a therapeutic target.
Identifiants
pubmed: 37924516
pii: S2211-1247(23)01375-X
doi: 10.1016/j.celrep.2023.113363
pii:
doi:
Substances chimiques
BAHCC1 protein, human
0
Proteins
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
113363Informations 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.