Repression of Runx2 function by TGF-beta through recruitment of class II histone deacetylases by Smad3.
Repression of Runx2 function by TGF-beta through recruitment of class II histone deacetylases by Smad3.
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发表时间：
2005
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通讯作者：
Jong Seok Kang;T. Alliston;R. Delston;R. Derynck
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作者：
Jong Seok Kang;T. Alliston;R. Delston;R. Derynck
转化生长因子-β（TGF-β）通过Smad 3抑制Runx 2（Cbfa 1）的功能来抑制成骨细胞分化。TGF-β/Smad 3抑制Runx 2功能的机制尚未得到表征。我们表明，TGF-β诱导组蛋白脱乙酰化，主要是组蛋白H4，在骨钙素启动子，这是抑制TGF-β，和组蛋白脱乙酰化所需的抑制Runx 2的TGF-β。这种抑制通过IIa类组蛋白脱乙酰基酶（HDAC）4和5的作用发生，HDAC 4和5通过与Smad 3相互作用被募集到Runx 2结合DNA序列处的Smad 3/Runx 2复合物。因此，HDAC 4或5是TGF-β介导的Runx 2功能的有效抑制所必需的，并且参与成骨细胞分化。我们的研究结果表明，IIa类HDACs作为辅阻遏物的TGF-β/Smad 3介导的转录抑制Runx 2功能分化成骨细胞，是成骨细胞分化的细胞内在调节因子。
Transforming growth factor-beta (TGF-beta) inhibits osteoblast differentiation through inhibition of the function of Runx2 (Cbfa1) by Smad3. The mechanism through which TGF-beta/Smad3 inhibits Runx2 function has not been characterized. We show that TGF-beta induces histone deacetylation, primarily of histone H4, at the osteocalcin promoter, which is repressed by TGF-beta, and that histone deacetylation is required for repression of Runx2 by TGF-beta. 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-beta-mediated inhibition of Runx2 function and is involved in osteoblast differentiation. Our results indicate that class IIa HDACs act as corepressors for TGF-beta/Smad3-mediated transcriptional repression of Runx2 function in differentiating osteoblasts and are cell-intrinsic regulators of osteoblast differentiation.