Acetylation of the yeast histone H4N terminus regulates its binding to heterochromatin protein SIR3
Acetylation of the yeast histone H4N terminus regulates its binding to heterochromatin protein SIR3
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DOI：
10.1074/jbc.m110532200
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发表时间：
2002-02-15
影响因子：
4.8
通讯作者：
Grunstein, M
中科院分区：
文献类型：
--
作者：
Carmen, AA;Milne, L;Grunstein, M
酵母端粒和沉默交配（HM）位点上的异染色质抑制邻近基因，并通过沉默信息调节因子（SIR蛋白）沿组蛋白的结合和传播形成。这涉及到SIR3的C端和组蛋白H4的N端之间的相互作用。由于H4在异染色质中是低乙酰化的，我们希望确定乙酰化是否参与调节SIR3和H4之间的接触。利用表面等离子体共振研究了赖氨酸Lys-5、Lys-8、Lys-12和Lys-16乙酰化的H4肽（残基1-34）与固定的SIR3蛋白片段（残基510-970）的结合。我们发现H4赖氨酸的乙酰化减少了114与SIRS的结合（K-a），从而使完全乙酰化的肽结合相对于未乙酰化的肽减少了近50倍。因此，通过影响SIR3-H4的结合，乙酰化可能调节异染色质的形成。这些数据有助于解释真核生物异染色质中组蛋白H4的低乙酰化状态。
Heterochromatin at yeast telomeres and silent mating (HM) loci represses adjacent genes and is formed by the binding and spreading of silencing information regulators (SIR proteins) along histones. This involves the interaction between the C terminus of SIR3 and the N terminus of histone H4. Since H4 is hypoacetylated in heterochromatin we wished to determine whether acetylation is involved in regulating the contacts between SIR3 and H4. Binding of H4 peptide (residues 1-34) acetylated at lysines Lys-5, Lys-8, Lys-12, and Lys-16 to an immobilized SIR3 protein fragment (residues 510-970) was investigated using surface plasmon resonance. We find that acetylation of H4 lysines reduces binding (K-a) of 114 to SIRS in a cumulative manner so that the fully acetylated peptide binding is decreased similar to50-fold relative to unacetylated peptide. Thus, by affecting SIR3-H4 binding, acetylation may regulate the formation of heterochromatin. These data help explain the hypoacetylated state of histone H4 in heterochromatin of eukaryotes.