Exploring the impact of dexamethasone on gene regulation in myeloma cells.
Journal
Life science alliance
ISSN: 2575-1077
Titre abrégé: Life Sci Alliance
Pays: United States
ID NLM: 101728869
Informations de publication
Date de publication:
09 2023
09 2023
Historique:
received:
01
06
2023
revised:
23
06
2023
accepted:
26
06
2023
medline:
3
8
2023
pubmed:
1
8
2023
entrez:
31
7
2023
Statut:
epublish
Résumé
Among glucocorticoids (GCs), dexamethasone (Dex) is widely used in treatment of multiple myelomas. However, despite a definite benefit, all patients relapse. Moreover, the molecular basis of glucocorticoid efficacy remains elusive. To determine genomic response to Dex in myeloma cells, we generated bulk and single-cell multi-omics data and high-resolution contact maps of active enhancers and target genes. We show that a minority of glucocorticoid receptor-binding sites are associated with enhancer activity gains, increased interaction loops, and transcriptional activity. We identified and characterized a predominant enhancer enriched in cohesin (RAD21) and more accessible upon Dex exposure. Analysis of four gene-specific networks revealed the importance of the CTCF-cohesin couple and the synchronization of regulatory sequence openings for efficient transcription in response to Dex. Notably, these epigenomic changes are associated with cell-to-cell transcriptional heterogeneity, in particular, lineage-specific genes. As consequences,
Identifiants
pubmed: 37524526
pii: 6/9/e202302195
doi: 10.26508/lsa.202302195
pmc: PMC10390781
pii:
doi:
Substances chimiques
Dexamethasone
7S5I7G3JQL
Glucocorticoids
0
Receptors, Glucocorticoid
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2023 Bessonneau-Gaborit et al.
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