Tracking Targets of Dynamic Super-Enhancers


Journal

Environmental health perspectives
ISSN: 1552-9924
Titre abrégé: Environ Health Perspect
Pays: United States
ID NLM: 0330411

Informations de publication

Date de publication:
06 2023
Historique:
medline: 14 6 2023
pubmed: 12 6 2023
entrez: 12 6 2023
Statut: ppublish

Résumé

Osteoclasts are major actors in the maintenance of bone homeostasis. The full functional maturation of osteoclasts from monocyte lineage cells is essential for the degradation of old/damaged bone matrix. Diuron is one of the most frequently encountered herbicides, particularly in water sources. However, despite a reported delayed ossification The objectives of this study were to first better characterize osteoclastogenesis by identifying genes that drive the differentiation of We performed chromatin immunoprecipitation (ChIP) against H3K27ac followed by ChIP-sequencing (ChIP-Seq) and RNA-sequencing (RNA-Seq) at different stages of differentiation of The combinatorial study of the epigenetic and transcriptional remodeling taking place during differentiation has revealed a very dynamic epigenetic profile that supports the expression of genes vital for osteoclast differentiation and function. In total, we identified 122 genes induced by dynamic super-enhancers at late days. Our data suggest that high concentration of diuron ( Exposure to high concentrations of diuron decreased the viability of MSCs and could therefore affect osteoblastic differentiation and bone mineralization. This pesticide also disrupted osteoclasts maturation by impairing the expression of cell-identity determining genes. Indeed, at sublethal concentrations, differences in the expression of these key genes were mild during the course of

Sections du résumé

BACKGROUND
Osteoclasts are major actors in the maintenance of bone homeostasis. The full functional maturation of osteoclasts from monocyte lineage cells is essential for the degradation of old/damaged bone matrix. Diuron is one of the most frequently encountered herbicides, particularly in water sources. However, despite a reported delayed ossification
OBJECTIVES
The objectives of this study were to first better characterize osteoclastogenesis by identifying genes that drive the differentiation of
METHODS
We performed chromatin immunoprecipitation (ChIP) against H3K27ac followed by ChIP-sequencing (ChIP-Seq) and RNA-sequencing (RNA-Seq) at different stages of differentiation of
RESULTS
The combinatorial study of the epigenetic and transcriptional remodeling taking place during differentiation has revealed a very dynamic epigenetic profile that supports the expression of genes vital for osteoclast differentiation and function. In total, we identified 122 genes induced by dynamic super-enhancers at late days. Our data suggest that high concentration of diuron (
DISCUSSION
Exposure to high concentrations of diuron decreased the viability of MSCs and could therefore affect osteoblastic differentiation and bone mineralization. This pesticide also disrupted osteoclasts maturation by impairing the expression of cell-identity determining genes. Indeed, at sublethal concentrations, differences in the expression of these key genes were mild during the course of

Identifiants

pubmed: 37307168
doi: 10.1289/EHP11690
pmc: PMC10259763
doi:

Substances chimiques

Diuron 9I3SDS92WY
Herbicides 0

Types de publication

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

Langues

eng

Sous-ensembles de citation

IM

Pagination

67007

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Auteurs

Robel A Tesfaye (RA)

CRCI2NA, INSERM UMR 1307, CNRS UMR 6075, Nantes University and Angers University, Nantes, France.
Cancéropole Grand-Ouest, réseau Epigénétique, Nantes, France.
EpiSAVMEN, Epigenetic consortium Pays de la Loire, France.

Melanie Lavaud (M)

CRCI2NA, INSERM UMR 1307, CNRS UMR 6075, Nantes University and Angers University, Nantes, France.

Céline Charrier (C)

CRCI2NA, INSERM UMR 1307, CNRS UMR 6075, Nantes University and Angers University, Nantes, France.

Bénédicte Brounais-Le Royer (B)

CRCI2NA, INSERM UMR 1307, CNRS UMR 6075, Nantes University and Angers University, Nantes, France.

Pierre-François Cartron (PF)

CRCI2NA, INSERM UMR 1307, CNRS UMR 6075, Nantes University and Angers University, Nantes, France.
LaBCT, Institut de Cancérologie de l'Ouest, Saint Herblain, France.
Cancéropole Grand-Ouest, réseau Epigénétique, Nantes, France.
EpiSAVMEN, Epigenetic consortium Pays de la Loire, France.

Franck Verrecchia (F)

CRCI2NA, INSERM UMR 1307, CNRS UMR 6075, Nantes University and Angers University, Nantes, France.

Marc Baud'huin (M)

CRCI2NA, INSERM UMR 1307, CNRS UMR 6075, Nantes University and Angers University, Nantes, France.

François Lamoureux (F)

CRCI2NA, INSERM UMR 1307, CNRS UMR 6075, Nantes University and Angers University, Nantes, France.

Steven Georges (S)

CRCI2NA, INSERM UMR 1307, CNRS UMR 6075, Nantes University and Angers University, Nantes, France.

Benjamin Ory (B)

CRCI2NA, INSERM UMR 1307, CNRS UMR 6075, Nantes University and Angers University, Nantes, France.
Cancéropole Grand-Ouest, réseau Epigénétique, Nantes, France.
EpiSAVMEN, Epigenetic consortium Pays de la Loire, France.

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