Repression of Runx 2 function by TGF-b through recruitment of class II histone deacetylases by Smad 3
Repression of Runx 2 function by TGF-b through recruitment of class II histone deacetylases by Smad 3
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发表时间：
2005
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通讯作者：
J. Kang;T. Alliston;R. Delston;R. Derynck
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作者：
J. Kang;T. Alliston;R. Delston;R. Derynck
转化生长因子-b通过抑制Smad3对Runx2(Cbfa1)的功能抑制成骨细胞的分化。转化生长因子-β/Smad3抑制Runx2功能的机制尚不清楚。我们发现，转化生长因子-β在骨钙素启动子处诱导组蛋白去乙酰化，主要是组蛋白H4，而组蛋白去乙酰化是被转化生长因子-β抑制Runx2所必需的。这种抑制是通过IIa类组蛋白脱乙酰酶(HDAC)4和5的作用发生的，这两个酶是通过与Smad3相互作用而招募到Runx2结合DNA序列上的Smad3/Runx2复合体的。因此，HDAC4或5是转化生长因子-b介导的有效抑制Runx2功能所必需的，并参与成骨细胞的分化。我们的结果表明，IIa类HDAC作为辅助抑制因子，通过转化生长因子-b/Smad3介导的转录抑制Runx2在成骨细胞分化中的功能，是成骨细胞分化的细胞内源性调节因子。《EMBO期刊》(2005)24,2543-2555。DOI：10.1038/sj.empallj.7600729；2005年6月30日在线发表主题类别：信号转导
Transforming growth factor-b (TGF-b) inhibits osteoblast differentiation through inhibition of the function of Runx2 (Cbfa1) by Smad3. The mechanism through which TGF-b/ Smad3 inhibits Runx2 function has not been characterized. We show that TGF-b induces histone deacetylation, primarily of histone H4, at the osteocalcin promoter, which is repressed by TGF-b, and that histone deacetylation is required for repression of Runx2 by TGF-b. This repression occurs through the action of the class IIa histone deacetylases (HDAC)4 and 5, which are recruited through interaction with Smad3 to the Smad3/Runx2 complex at the Runx2-binding DNA sequence. Accordingly, HDAC4 or 5 is required for efficient TGF-b-mediated inhibition of Runx2 function and is involved in osteoblast differentiation. Our results indicate that class IIa HDACs act as corepressors for TGF-b/Smad3-mediated transcriptional repression of Runx2 function in differentiating osteoblasts and are cell-intrinsic regulators of osteoblast differentiation. The EMBO Journal (2005) 24, 2543–2555. doi:10.1038/ sj.emboj.7600729; Published online 30 June 2005 Subject Categories: signal transduction