Yohei Abe, Eric R Kofman, Maria Almeida, Zhengyu Ouyang, Filipa Ponte, Jasmine R Mueller, Grisel Cruz-Becerra, Mashito Sakai, Thomas A Prohaska, Nathanael J Spann, Ana Resende-Coelho, Jason S Seidman, Joshua D Stender, Havilah Taylor, Weiwei Fan, Verena M Link, Isidoro Cobo, Johannes C M Schlachetzki, Takao Hamakubo, Kristen Jepsen, Juro Sakai, Michael Downes, Ronald M Evans, Gene W Yeo, James T Kadonaga, Stavros C Manolagas, Michael G Rosenfeld, Christopher K Glass
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 κB (RANK) converts the NCoR/HDAC3 co-repressor complex to a co-activator of AP-1 and NF-κB 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...
September 14, 2023: Molecular Cell