ATF2 is required for amino acid-regulated transcription by orchestrating specific histone acetylation.
ATF2 is required for amino acid-regulated transcription by orchestrating specific histone acetylation.
复制标题
通过修复特定的组蛋白乙酰化，需要ATF2进行氨基酸调节的转录。
DOI：
10.1093/nar/gkm038
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发表时间：
2007
影响因子：
14.9
通讯作者：
Fafournoux, Pierre
中科院分区：
文献类型：
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作者：
Bruhat, Alain;Cherasse, Yoan;Maurin, Anne-Catherine;Breitwieser, Wolfgang;Parry, Laurent;Deval, Christiane;Jones, Nic;Jousse, Celine;Fafournoux, Pierre
CHOP(一种CCAAT/增强子结合蛋白相关基因)在转录水平上的激活涉及激活转录因子2(ATF2)和激活转录因子4(ATF4)，ATF4与启动子内的氨基酸反应元件(AARE)结合。利用染色质免疫沉淀的方法，我们报道了在体内，磷酸化ATF2和ATF4与CHOP AARE的结合与组蛋白H4和H2B在氨基酸饥饿时的乙酰化反应有关。时程分析表明，ATF2的磷酸化先于组蛋白乙酰化、ATF4结合和CHOP mRNA的增加。我们还表明，ATF4结合和组蛋白乙酰化是氨基酸饥饿时CHOP诱导所必需的两个独立事件。利用ATF2缺失的小鼠胚胎成纤维细胞，我们证明了ATF2在活体中组蛋白H4和组蛋白H_2B的乙酰化过程中是必不可少的。ATF2在组蛋白H4乙酰化中的作用依赖于它与AARE的结合，并且可以扩展到其他氨基酸调控的基因。因此，ATF2参与促进染色质结构的改变，以增强一些氨基酸调节基因的转录。
The transcriptional activation of CHOP (a CCAAT/enhancer-binding protein-related gene) by amino acid deprivation involves the activating transcription factor 2 (ATF2) and the activating transcription factor 4 (ATF4) binding the amino acid response element (AARE) within the promoter. Using a chromatin immunoprecipitation approach, we report that in vivo binding of phospho-ATF2 and ATF4 to CHOP AARE are associated with acetylation of histones H4 and H2B in response to amino acid starvation. A time course analysis reveals that ATF2 phosphorylation precedes histone acetylation, ATF4 binding and the increase in CHOP mRNA. We also show that ATF4 binding and histone acetylation are two independent events that are required for the CHOP induction upon amino acid starvation. Using ATF2-deficient mouse embryonic fibroblasts, we demonstrate that ATF2 is essential in the acetylation of histone H4 and H2B in vivo. The role of ATF2 on histone H4 acetylation is dependent on its binding to the AARE and can be extended to other amino acid regulated genes. Thus, ATF2 is involved in promoting the modification of the chromatin structure to enhance the transcription of a number of amino acid-regulated genes.