Nuclear receptor repression mediated by a complex containing SMRT, mSin3A, and histone deacetylase
Nuclear receptor repression mediated by a complex containing SMRT, mSin3A, and histone deacetylase
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DOI：
10.1016/s0092-8674(00)80218-4
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发表时间：
1997-05-02
期刊：
影响因子：
64.5
通讯作者：
Evans, RM
中科院分区：
文献类型：
--
作者：
Nagy, L;Kao, HY;Evans, RM
转录辅阻遏子SMRT和N-COR作为维甲酸和甲状腺激素受体的沉默介体发挥作用。在这里，我们证明了SMRT和N-COR直接与mSin3A相互作用，mSin3A是Mad-Max异源二聚体的辅阻遏子，也是酵母全局转录抑制子Sin3p的同源物。此外，我们还证明了最近鉴定的组蛋白脱乙酰基酶1(HDAC1)与Sin3A和SMRT相互作用，形成多亚基阻遏复合体。与这一模型一致，我们发现HDAC抑制剂与维甲酸协同刺激激素反应基因和髓系白血病(HL-60)细胞的分化。这项工作建立了bHLH-Zip蛋白和核受体的抑制通路的趋同，并表明这种类型的调控可能比之前怀疑的更广泛保守。
The transcriptional corepressors SMRT and N-CoR function as silencing mediators for retinoid and thyroid hormone receptors. Here we show that SMRT and N-CoR directly interact with mSin3A, a corepressor for the Mad-Max heterodimer and a homolog of the yeast global-transcriptional repressor Sin3p. In addition, we demonstrate that the recently characterized histone deacetylase 1 (HDAC1) interacts with Sin3A and SMRT to form a multisubunit repressor complex. Consistent with this model, we find that HDAC inhibitors synergize with retinoic acid to stimulate hormone-responsive genes and differentiation of myeloid leukemia (HL-60) cells. This work establishes a convergence of repression pathways for bHLH-Zip proteins and nuclear receptors and suggests this type of regulation may be more widely conserved than previously suspected.