Replication-independent histone deposition by the HIR complex and Asf1

Replication-independent histone deposition by the HIR complex and Asf1
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DOI:
10.1016/j.cub.2005.10.053
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发表时间:
2005-11-22
期刊:
影响因子:
9.2
通讯作者:
Kaufman, PD
Kaufman, PD
中科院分区:
生物学1区
文献类型:
--
作者:
Green, EM;Antczak, AJ;Kaufman, PD

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组蛋白在DNA上的有序沉积由保守的组装复合物介导,包括染色质组装因子-1(CAF-1)和Hir蛋白[1-4]。CAF-1和Hir蛋白在体内以不同但功能上重叠的组蛋白沉积途径起作用[5,6]。Hir蛋白和CAF-1共有一个共同的伴侣,即高度保守的组蛋白H3/H4结合蛋白Asf 1,其结合CAF-1的中间亚基以及Hir蛋白[7-11]。Asf 1与新合成的组蛋白H3/H4结合[12],该复合物通过CAF-1刺激组蛋白沉积[7,11,12]。在酵母中,Asf 1是Hir蛋白对基因沉默的贡献所必需的[7,13]。在这里,我们证明,HIM,Hir 2,Hir 3,和Hpc 2包括HIR复合物,其与组蛋白沉积蛋白Asf 1共纯化。HIR复合物和Asf 1存款组蛋白一起以复制独立的方式到DNA上。HIR复合物和Asf 1的组蛋白沉积受到抑制HIR结合的Asf 1突变的损害。这些数据表明,HIR复合物和Asf 1蛋白一起作为一个保守的真核细胞通路,在整个细胞周期中的组蛋白替代功能。
The orderly deposition of histones onto DNA is mediated by conserved assembly complexes, including chromatin assembly factor-1 (CAF-1) and the Hir proteins [1-4]. CAF-1 and the Hir proteins operate in distinct but functionally overlapping histone deposition pathways in vivo [5, 6]. The Hir proteins and CAF-1 share a common partner, the highly conserved histone H3/H4 binding protein Asf1, which binds the middle subunit of CAF-1 as well as to Hir proteins [7-11]. Asf1 binds to newly synthesized histones H3/H4 [12], and this complex stimulates histone deposition by CAF-1 [7,11,12]. In yeast, Asf1 is required for the contribution of the Hir proteins to gene silencing [7, 13]. Here, we demonstrate that HIM, Hir2, Hir3, and Hpc2 comprise the HIR complex, which copurifies with the histone deposition protein Asf1. Together, the HIR complex and Asf1 deposit histones onto DNA in a replication-independent manner. Histone deposition by the HIR complex and Asf1 is impaired by a mutation in Asf1 that inhibits HIR binding. These data indicate that the HIR complex and Asf1 proteins function together as a conserved eukaryotic pathway for histone replacement throughout the cell cycle.