CHD4 Is a Peripheral Component of the Nucleosome Remodeling and Deacetylase Complex
CHD4 Is a Peripheral Component of the Nucleosome Remodeling and Deacetylase Complex
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DOI：
10.1074/jbc.m115.707018
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发表时间：
2016-07-22
影响因子：
4.8
通讯作者：
Mackay, Joel P.
中科院分区：
文献类型：
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作者：
Low, Jason K. K.;Webb, Sarah R.;Mackay, Joel P.
染色质重塑酶的作用是动态调节基因的可及性。在许多情况下，这些酶作为大型多组分复合物发挥作用，通常包含中央 ATP 依赖性 Snf2 家族解旋酶，该解旋酶装饰有数量可变的调节亚基。核小体重塑和脱乙酰酶（NuRD）复合物对于高等生物的正常发育至关重要，就是这样一种大分子机器。 NuRD 复合体包含类似的 10 个亚基，包括组蛋白脱乙酰酶 1 和 2（HDAC1 和 HDAC2），并由 CHD 家族重塑酶（最常见的是 CHD4（染色质结构域解旋酶 DNA 结合蛋白 4））的存在来定义。现有范例认为 CHD4 充当构建综合体的中心枢纽。我们在这里表明，这种范式实际上并不成立，并且 CHD4 是 NuRD 复合体的外围组件。缺乏CHD4但具有HDAC活性的复合物可以作为稳定的物种存在。将重组 CHD4 添加到该核小体脱乙酰酶复合物中，可重建具有核小体重塑活性的 NuRD 复合物。这些数据有助于我们理解 NuRD 复合体的架构。
Chromatin remodeling enzymes act to dynamically regulate gene accessibility. In many cases, these enzymes function as large multicomponent complexes that in general comprise a central ATP-dependent Snf2 family helicase that is decorated with a variable number of regulatory subunits. The nucleosome remodeling and deacetylase (NuRD) complex, which is essential for normal development in higher organisms, is one such macromolecular machine. The NuRD complex comprises similar to 10 subunits, including the histone deacetylases 1 and 2 (HDAC1 and HDAC2), and is defined by the presence of a CHD family remodeling enzyme, most commonly CHD4 (chromodomain helicase DNA-binding protein 4). The existing paradigm holds that CHD4 acts as the central hub upon which the complex is built. We show here that this paradigm does not, in fact, hold and that CHD4 is a peripheral component of the NuRD complex. A complex lacking CHD4 that has HDAC activity can exist as a stable species. The addition of recombinant CHD4 to this nucleosome deacetylase complex reconstitutes a NuRD complex with nucleosome remodeling activity. These data contribute to our understanding of the architecture of the NuRD complex.