The high mobility group protein HMO1 functions as a linker histone in yeast.
The high mobility group protein HMO1 functions as a linker histone in yeast.
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DOI：
10.1186/s13072-016-0062-8
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发表时间：
2016
影响因子：
3.9
通讯作者：
Grove A
中科院分区：
文献类型：
--
作者：
Panday A;Grove A
真核染色质由不同长度的DNA连接的核小体核心颗粒组成。组蛋白H1与连接体DNA结合以稳定高阶染色质结构并调节调节因子接近其核小体目标的能力。在酿酒酵母中，与H1序列相似性最大的蛋白是Hho1p。然而，在营养生长期间，hho1∆细胞没有表现出任何可识别的细胞生长缺陷或大量染色质结构的变化，而这些变化是多细胞真核生物在H1被耗尽时染色质的特征。相比之下，据报道，酵母高迁移率组（HMGB）蛋白HMO1使染色质致密，HMO1∆细胞中核酸酶敏感性增加。与脊椎动物HMGB蛋白相比，HMO1具有不同寻常的结构域结构，因为HMG结构域后面是富含赖氨酸的延伸，而不是酸性结构域。我们在这里提出了HMO1在染色质压实方面起H1作用的假设，并且该功能需要富含赖氨酸的延伸。我们在这里展示了HMO1实现了连接组蛋白的这一功能。对于组蛋白H1，染色质压缩需要其基本的c端结构域，我们发现HMO1也是如此，因为删除其c端富含赖氨酸的延伸会使染色质核酸酶敏感。在rDNA上，需要同时删除HMO1和Hho1p才能显著增加核酸酶的敏感性。人组蛋白H1的表达完全逆转了从hmo1∆细胞中分离的染色质的核酸酶敏感性特征。虽然在hmo1缺失造成的更动态的染色质环境中，与DNA双链断裂修复相关的染色质重塑事件发生得更快，但人类组蛋白H1的表达导致染色质重塑和双链断裂修复，与在野生型细胞中观察到的相似。我们的数据表明酿酒酵母HMO1保护连接体DNA免受核酸酶的酶切，这也是哺乳动物连接体组蛋白H1的特征。值得注意的是，与HMO1的关联创造了一个不太动态的染色质环境，依赖于其赖氨酸丰富的结构域。HMO1具有连接组蛋白功能，这对染色质结构和功能的研究以及在染色质压实中起作用的蛋白质的进化具有重要意义。
Eukaryotic chromatin consists of nucleosome core particles connected by linker DNA of variable length. Histone H1 associates with the linker DNA to stabilize the higher-order chromatin structure and to modulate the ability of regulatory factors to access their nucleosomal targets. In Saccharomyces cerevisiae, the protein with greatest sequence similarity to H1 is Hho1p. However, during vegetative growth, hho1∆ cells do not show any discernible cell growth defects or the changes in bulk chromatin structure that are characteristic of chromatin from multicellular eukaryotes in which H1 is depleted. In contrast, the yeast high mobility group (HMGB) protein HMO1 has been reported to compact chromatin, as evidenced by increased nuclease sensitivity in hmo1∆ cells. HMO1 has an unusual domain architecture compared to vertebrate HMGB proteins in that the HMG domains are followed by a lysine-rich extension instead of an acidic domain. We address here the hypothesis that HMO1 serves the role of H1 in terms of chromatin compaction and that this function requires the lysine-rich extension. We show here that HMO1 fulfills this function of a linker histone. For histone H1, chromatin compaction requires its basic C-terminal domain, and we find that the same pertains to HMO1, as deletion of its C-terminal lysine-rich extension renders chromatin nuclease sensitive. On rDNA, deletion of both HMO1 and Hho1p is required for significantly increased nuclease sensitivity. Expression of human histone H1 completely reverses the nuclease sensitivity characteristic of chromatin isolated from hmo1∆ cells. While chromatin remodeling events associated with repair of DNA double-strand breaks occur faster in the more dynamic chromatin environment created by the hmo1 deletion, expression of human histone H1 results in chromatin remodeling and double-strand break repair similar to that observed in wild-type cells. Our data suggest that S. cerevisiae HMO1 protects linker DNA from nuclease digestion, a property also characteristic of mammalian linker histone H1. Notably, association with HMO1 creates a less dynamic chromatin environment that depends on its lysine-rich domain. That HMO1 has linker histone function has implications for investigations of chromatin structure and function as well as for evolution of proteins with roles in chromatin compaction.