Histone H2AX phosphorylation in response to changes in chromatin structure induced by altered osmolarity
Histone H2AX phosphorylation in response to changes in chromatin structure induced by altered osmolarity
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DOI：
10.1093/mutage/gen064
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发表时间：
2009-03-01
期刊：
影响因子：
2.7
通讯作者：
Limoli, Charles L.
中科院分区：
文献类型：
--
作者：
Baure, Jennifer;Izadi, Atefeh;Limoli, Charles L.
DNA链断裂触发组蛋白H2AX（即γ-H2AX）的显著磷酸化。虽然DNA双链断裂（DSB）为这一事件提供了强烈的刺激，但染色质中伴随的结构改变可能代表了激发γ-H2AX的实际信号。我们的数据表明，染色质结构的变化足以引起广泛的γ-H2AX形成的DNA链断裂的相对缺乏。经过低渗（0.05 M）处理的细胞表现出γ-H2AX水平，其相当于在诱导80 - 200 DNA DSB（即2 - 5戈伊）后发现的水平。尽管磷酸化显著增加，但细胞存活保持相对不受影响（<10%细胞毒性），并且细胞凋亡没有显著增加。核染色图谱表明，在张力改变下诱导的γ-H2AX阳性细胞表现出不同水平的染色，范围从均匀的泛染色到离散的点状病灶，更具有DNA链断裂的特征。在相对不存在DNA链断裂的情况下，在改变的张力下诱导显著的γ-H2AX形成的能力表明，这种组蛋白修饰响应于染色质结构的变化而进化。
DNA strand breaks trigger marked phosphorylation of histone H2AX (i.e. gamma-H2AX). While DNA double-strand breaks (DSBs) provide a strong stimulus for this event, the accompanying structural alterations in chromatin may represent the actual signal that elicits gamma-H2AX. Our data show that changes in chromatin structure are sufficient to elicit extensive gamma-H2AX formation in the relative absence of DNA strand breaks. Cells subjected to hypotonic (0.05 M) treatment exhibit gamma-H2AX levels that are equivalent to those found after the induction of 80-200 DNA DSBs (i.e. 2-5 Gy). Despite this significant increase in phosphorylation, cell survival remains relatively unaffected (< 10% cytotoxicity), and there is no significant increase in apoptosis. Nuclear staining profiles indicate that gamma-H2AX-positive cells induced under altered tonicity exhibit variable levels of staining, ranging from uniform pan staining to discrete punctate foci more characteristic of DNA strand breakage. The capability to induce significant gamma-H2AX formation under altered tonicity in the relative absence of DNA strand breaks suggests that this histone modification evolved in response to changes in chromatin structure.