Show simple item record

Wnt Protein Signaling Reduces Nuclear Acetyl-CoA Levels to Suppress Gene Expression during Osteoblast Differentiation.

dc.contributor.author Karner, CM
dc.contributor.author Esen, E
dc.contributor.author Chen, J
dc.contributor.author Hsu, FF
dc.contributor.author Turk, J
dc.contributor.author Long, F
dc.coverage.spatial United States
dc.date.accessioned 2016-05-13T14:09:03Z
dc.date.issued 2016-06-17
dc.identifier http://www.ncbi.nlm.nih.gov/pubmed/27129247
dc.identifier M115.708578
dc.identifier.uri https://hdl.handle.net/10161/12019
dc.description.abstract Developmental signals in metazoans play critical roles in inducing cell differentiation from multipotent progenitors. The existing paradigm posits that the signals operate directly through their downstream transcription factors to activate expression of cell type-specific genes, which are the hallmark of cell identity. We have investigated the mechanism through which Wnt signaling induces osteoblast differentiation in an osteoblast-adipocyte bipotent progenitor cell line. Unexpectedly, Wnt3a acutely suppresses the expression of a large number of genes while inducing osteoblast differentiation. The suppressed genes include Pparg and Cebpa, which encode adipocyte-specifying transcription factors and suppression of which is sufficient to induce osteoblast differentiation. The large scale gene suppression induced by Wnt3a corresponds to a global decrease in histone acetylation, an epigenetic modification that is associated with gene activation. Mechanistically, Wnt3a does not alter histone acetyltransferase or deacetylase activities but, rather, decreases the level of acetyl-CoA in the nucleus. The Wnt-induced decrease in histone acetylation is independent of β-catenin signaling but, rather, correlates with suppression of glucose metabolism in the tricarboxylic acid cycle. Functionally, preventing histone deacetylation by increasing nucleocytoplasmic acetyl-CoA levels impairs Wnt3a-induced osteoblast differentiation. Thus, Wnt signaling induces osteoblast differentiation in part through histone deacetylation and epigenetic suppression of an alternative cell fate.
dc.language eng
dc.relation.ispartof J Biol Chem
dc.relation.isversionof 10.1074/jbc.M115.708578
dc.subject Wnt signaling
dc.subject adipogenesis
dc.subject glucose metabolism
dc.subject histone acetylation
dc.subject osteoblast
dc.subject Acetyl Coenzyme A
dc.subject Acetylation
dc.subject Animals
dc.subject Cell Differentiation
dc.subject Cell Line
dc.subject Cell Nucleus
dc.subject Citric Acid
dc.subject Citric Acid Cycle
dc.subject Gene Expression
dc.subject Gene Silencing
dc.subject Glucose
dc.subject Histones
dc.subject Mice
dc.subject Osteoblasts
dc.subject Protein Processing, Post-Translational
dc.subject Wnt Signaling Pathway
dc.subject Wnt3A Protein
dc.title Wnt Protein Signaling Reduces Nuclear Acetyl-CoA Levels to Suppress Gene Expression during Osteoblast Differentiation.
dc.type Journal article
pubs.author-url http://www.ncbi.nlm.nih.gov/pubmed/27129247
pubs.begin-page 13028
pubs.end-page 13039
pubs.issue 25
pubs.organisational-group Basic Science Departments
pubs.organisational-group Cell Biology
pubs.organisational-group Clinical Science Departments
pubs.organisational-group Duke
pubs.organisational-group Orthopaedics
pubs.organisational-group School of Medicine
pubs.publication-status Published
pubs.volume 291
dc.identifier.eissn 1083-351X


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record