β-Catenin Preserves the Stem State of Murine Bone Marrow Stromal Cells Through Activation of EZH2.
ACTIN-POLYMERIZATION
ADIPOCYTE
ChIP-Seq
H3K27me3
OSTEOBLAST
ROCK-INHIBITION
RhoA
Wnt
Journal
Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research
ISSN: 1523-4681
Titre abrégé: J Bone Miner Res
Pays: United States
ID NLM: 8610640
Informations de publication
Date de publication:
06 2020
06 2020
Historique:
received:
18
06
2019
revised:
23
01
2020
accepted:
29
01
2020
pubmed:
6
2
2020
medline:
29
7
2021
entrez:
6
2
2020
Statut:
ppublish
Résumé
During bone marrow stromal cell (BMSC) differentiation, both Wnt signaling and the development of a rigid cytoskeleton promote commitment to the osteoblastic over adipogenic lineage. β-catenin plays a critical role in the Wnt signaling pathway to facilitate downstream effects on gene expression. We show that β-catenin was additive with cytoskeletal signals to prevent adipogenesis, and β-catenin knockdown promoted adipogenesis even when the actin cytoskeleton was depolymerized. β-catenin also prevented osteoblast commitment in a cytoskeletal-independent manner, with β-catenin knockdown enhancing lineage commitment. Chromatin immunoprecipitation (ChIP)-sequencing demonstrated binding of β-catenin to the promoter of enhancer of zeste homolog 2 (EZH2), a key component of the polycomb repressive complex 2 (PRC2) complex that catalyzes histone methylation. Knockdown of β-catenin reduced EZH2 protein levels and decreased methylated histone 3 (H3K27me3) at osteogenic loci. Further, when EZH2 was inhibited, β-catenin's anti-differentiation effects were lost. These results indicate that regulating EZH2 activity is key to β-catenin's effects on BMSCs to preserve multipotentiality. © 2020 American Society for Bone and Mineral Research.
Identifiants
pubmed: 32022326
doi: 10.1002/jbmr.3975
pmc: PMC7295671
mid: NIHMS1561599
doi:
Substances chimiques
CTNNB1 protein, mouse
0
Catenins
0
beta Catenin
0
Enhancer of Zeste Homolog 2 Protein
EC 2.1.1.43
Ezh2 protein, mouse
EC 2.1.1.43
Polycomb Repressive Complex 2
EC 2.1.1.43
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
1149-1162Subventions
Organisme : NICHD NIH HHS
ID : P2C HD086843
Pays : United States
Organisme : NIGMS NIH HHS
ID : P20 GM103408
Pays : United States
Organisme : NIGMS NIH HHS
ID : P20 GM109095
Pays : United States
Organisme : NIH HHS
ID : P20GM103408
Pays : United States
Organisme : NIAMS NIH HHS
ID : AR049069
Pays : United States
Organisme : NIAMS NIH HHS
ID : R01 AR049069
Pays : United States
Organisme : NIAMS NIH HHS
ID : R01 AR073264
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG059923
Pays : United States
Organisme : NIH HHS
ID : P20GM109095
Pays : United States
Organisme : NIAMS NIH HHS
ID : R01 AR066616
Pays : United States
Organisme : NIAMS NIH HHS
ID : R01 AR075803
Pays : United States
Organisme : NIAMS NIH HHS
ID : AR066616
Pays : United States
Informations de copyright
© 2020 American Society for Bone and Mineral Research.
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