| First Author | Abe Y | Year | 2023 |
| Journal | Mol Cell | Volume | 83 |
| Issue | 19 | Pages | 3421-3437.e11 |
| PubMed ID | 37751740 | Mgi Jnum | J:359899 |
| Mgi Id | MGI:7542860 | Doi | 10.1016/j.molcel.2023.08.029 |
| Citation | Abe Y, et al. (2023) RANK ligand converts the NCoR/HDAC3 co-repressor to a PGC1beta- and RNA-dependent co-activator of osteoclast gene expression. Mol Cell 83(19):3421-3437.e11 |
| abstractText | The nuclear receptor co-repressor (NCoR) complex mediates transcriptional repression dependent on histone deacetylation by histone deacetylase 3 (HDAC3) as a component of the complex. Unexpectedly, we found that signaling by the receptor activator of nuclear factor kappaB (RANK) converts the NCoR/HDAC3 co-repressor complex to a co-activator of AP-1 and NF-kappaB target genes that are required for mouse osteoclast differentiation. Accordingly, the dominant function of NCoR/HDAC3 complexes in response to RANK signaling is to activate, rather than repress, gene expression. Mechanistically, RANK signaling promotes RNA-dependent interaction of the transcriptional co-activator PGC1beta with the NCoR/HDAC3 complex, resulting in the activation of PGC1beta and inhibition of HDAC3 activity for acetylated histone H3. Non-coding RNAs Dancr and Rnu12, which are associated with altered human bone homeostasis, promote NCoR/HDAC3 complex assembly and are necessary for RANKL-induced osteoclast differentiation in vitro. These findings may be prototypic for signal-dependent functions of NCoR in other biological contexts. |
