{"doi":"10.1016/j.molcel.2023.08.029","title":"RANK ligand converts the NCoR/HDAC3 co-repressor to a PGC1β- and RNA-dependent co-activator of osteoclast gene expression","abstract":"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. Mechanistically, RANK signaling promotes RNA-dependent interaction of the transcriptional co-activator PGC1β with the NCoR/HDAC3 complex, resulting in the activation of PGC1β 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.","journal":"Molecular Cell","year":2023,"id":328414,"datarank":0.7470311660592137,"base_score":3.1780538303479458,"endowment":3.1780538303479458,"self_citation_contribution":0.47670807455219194,"citation_network_contribution":0.27032309150702183,"self_endowment_contribution":0.47670807455219194,"citer_contribution":0.27032309150702183,"corpus_percentile":null,"corpus_rank":null,"citation_count":23,"citer_count":19,"citers_with_citation_signal":12,"citers_with_endowment":12,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9523,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":80490,"name":"Eric Kofman","orcid":"0000-0001-5462-9099","position":1,"is_corresponding":false},{"id":237879,"name":"Maria Almeida","orcid":"0000-0002-6722-9200","position":2,"is_corresponding":false},{"id":80476,"name":"Zhengyu Ouyang","orcid":null,"position":3,"is_corresponding":false},{"id":281433,"name":"Filipa Ponte","orcid":"0000-0001-9713-3640","position":4,"is_corresponding":false},{"id":549995,"name":"Jasmine R. 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