组蛋白去乙酰化酶 1 的乙酰化调节 NuRD 核心抑制复合物的活性。
Acetylation of histone deacetylase 1 regulates NuRD corepressor complex activity.
机构信息
Department of Anatomy and Cell Biology, College of Medicine, University of Florida, Gainesville, FL 32610, USA.
出版信息
J Biol Chem. 2012 Nov 23;287(48):40279-91. doi: 10.1074/jbc.M112.349704. Epub 2012 Sep 25.
BACKGROUND
HDAC1-containing NuRD complex is required for GATA-1-mediated repression and activation.
RESULTS
GATA-1 associated with acetylated HDAC1-containing NuRD complex, which has no deacetylase activity, for gene activation.
CONCLUSION
Acetylated HDAC1 converts NuRD complex from a repressor to an activator during GATA-1-directed erythroid differentiation program.
SIGNIFICANCE
HDAC1 acetylation may function as a master regulator for the activity of HDAC1 containing complexes. Histone deacetylases (HDACs) play important roles in regulating cell proliferation and differentiation. The HDAC1-containing NuRD complex is generally considered as a corepressor complex and is required for GATA-1-mediated repression. However, recent studies also show that the NuRD complex is involved in GATA-1-mediated gene activation. We tested whether the GATA-1-associated NuRD complex loses its deacetylase activity and commits the GATA-1 complex to become an activator during erythropoiesis. We found that GATA-1-associated deacetylase activity gradually decreased upon induction of erythroid differentiation. GATA-1-associated HDAC1 is increasingly acetylated after differentiation. It has been demonstrated earlier that acetylated HDAC1 has no deacetylase activity. Indeed, overexpression of an HDAC1 mutant, which mimics acetylated HDAC1, promotes GATA-1-mediated transcription and erythroid differentiation. Furthermore, during erythroid differentiation, acetylated HDAC1 recruitment is increased at GATA-1-activated genes, whereas it is significantly decreased at GATA-1-repressed genes. Interestingly, deacetylase activity is not required for Mi2 remodeling activity, suggesting that remodeling activity may be required for both activation and repression. Thus, our data suggest that NuRD can function as a coactivator or repressor and that acetylated HDAC1 converts the NuRD complex from a repressor to an activator during GATA-1-directed erythroid differentiation.
背景
HDAC1 包含的 NuRD 复合物对于 GATA-1 介导的抑制和激活是必需的。
结果
GATA-1 与乙酰化的含有 NuRD 复合物的 HDAC1 相关联，该复合物没有脱乙酰酶活性，可用于基因激活。
结论
在 GATA-1 指导的红细胞分化程序中，乙酰化的 HDAC1 将 NuRD 复合物从抑制物转化为激活物。
意义
HDAC1 乙酰化可能作为含有 HDAC1 的复合物活性的主调控因子。组蛋白脱乙酰酶（HDACs）在调节细胞增殖和分化中起着重要作用。含 HDAC1 的 NuRD 复合物通常被认为是一种核心抑制剂复合物，并且是 GATA-1 介导的抑制所必需的。然而，最近的研究也表明，NuRD 复合物参与 GATA-1 介导的基因激活。我们测试了 GATA-1 相关的 NuRD 复合物是否在红细胞生成过程中失去其脱乙酰酶活性并促使 GATA-1 复合物成为激活剂。我们发现，在诱导红细胞分化时，GATA-1 相关的脱乙酰酶活性逐渐降低。分化后，GATA-1 相关的 HDAC1 被乙酰化。早期的研究表明，乙酰化的 HDAC1 没有脱乙酰酶活性。事实上，过表达模拟乙酰化 HDAC1 的 HDAC1 突变体可促进 GATA-1 介导的转录和红细胞分化。此外，在红细胞分化过程中，乙酰化的 HDAC1 在 GATA-1 激活的基因上的募集增加，而在 GATA-1 抑制的基因上的募集显著减少。有趣的是，脱乙酰酶活性不是 Mi2 重塑活性所必需的，这表明重塑活性可能既需要激活也需要抑制。因此，我们的数据表明，NuRD 可以作为共激活剂或抑制剂发挥作用，并且在 GATA-1 指导的红细胞分化过程中，乙酰化的 HDAC1 将 NuRD 复合物从抑制剂转化为激活剂。
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