RANK ligand converts the NCoR/HDAC3 co-repressor to a PGC1(3-and RNA-dependent co-activator of osteoclast gene expression

被引：12

作者：

Abe, Yohei ^{[1
]}

Kofman, Eric R. ^{[1
,2
,3
]}

Almeida, Maria ^{[4
,5
,6
]}

Ouyang, Zhengyu ^{[1
]}

Ponte, Filipa

Mueller, Jasmine R. ^{[1
,2
,3
]}

Cruz-Becerra, Grisel ^{[7
]}

Sakai, Mashito ^{[1
,8
]}

Prohaska, Thomas A. ^{[9
]}

Spann, Nathanael J. ^{[1
]}

Resende-Coelho, Ana ^{[4
]}

Seidman, Jason S. ^{[1
]}

Stender, Joshua D. ^{[1
]}

Taylor, Havilah

Fan, Weiwei ^{[10
]}

Link, Verena M. ^{[1
,11
]}

Cobo, Isidoro ^{[1
]}

Schlachetzki, Johannes C. M. ^{[1
]}

Hamakubo, Takao ^{[12
]}

Jepsen, Kristen ^{[3
]}

Sakai, Juro ^{[13
,14
]}

Downes, Michael

Evans, Ronald M. ^{[10
]}

Yeo, Gene W. ^{[1
,2
,3
]}

Kadonaga, James T.

Manolagas, Stavros C. ^{[4
]}

Rosenfeld, Michael G. ^{[5
,6
]}

Glass, Christopher K. ^{[1
,9
]}

机构：

[1] Univ Calif San Diego, Dept Cellular & Mol Med, La Jolla, CA 92093 USA

[2] Univ Calif San Diego, Stem Cell Program, La Jolla, CA 92093 USA

[3] Univ Calif San Diego, Inst Genom Med, La Jolla, CA 92093 USA

[4] Univ Arkansas Med Sci, Ctr Osteoporosis & Metab Bone Dis, Div Endocrinol & Metab, Little Rock, AR 72205 USA

[5] Univ Arkansas Med Sci, Dept Orthoped Surg, Little Rock, AR 72205 USA

[6] Cent Arkansas Vet Healthcare Syst, Little Rock, AR 72205 USA

[7] Univ Calif San Diego, Dept Mol Biol, La Jolla, CA 92093 USA

[8] Nippon Med Coll Hosp, Biochem & Mol Biol, Tokyo 1138602, Japan

[9] Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA

[10] Salk Inst Biol Studies, Gene Express Lab, La Jolla, CA 92037 USA

[11] Ludwig Maximilians Univ Munchen, Fac Biol, Dept 2, D-82152 Planegg Martinsried, Germany

[12] Nippon Med Sch, Inst Adv Med Sci, Dept Prot Prot Interact Res, Tokyo 1138602, Japan

[13] Univ Tokyo, Res Ctr Adv Sci & Technol, Div Metab Med, Tokyo 1538904, Japan

[14] Tohoku Univ, Div Mol Physiol & Metab, Grad Sch Med, Sendai 9808575, Japan

来源：

MOLECULAR CELL | 2023年 / 83卷 / 19期

基金：

日本学术振兴会;

关键词：

NF-KAPPA-B; TRANSCRIPTION FACTOR; BINDING PROTEINS; DIFFERENTIATION; MACROPHAGE; HDAC3; COREPRESSOR; METABOLISM; REGULATOR; DISCOVERY;

D O I：

10.1016/j.molcel.2023.08.029

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The nuclear receptor co-repressor (NCoR) complex mediates transcriptional repression dependent on his tone deacetylation by histone deacetylase 3 (HDAC3) as a component of the complex. Unexpectedly, we found that signaling by the receptor activator of nuclear factor kB (RANK) converts the NCoR/HDAC3 co repressor complex to a co-activator of AP-1 and NF-kB 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 PGC1(3 with the NCoR/HDAC3 complex, resulting in the activation of PGC1(3 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.

引用

页码：3421 / +

页数：29

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