Inheritance of Stress-Induced, ATF-2-Dependent Epigenetic Change
Inheritance of Stress-Induced, ATF-2-Dependent Epigenetic Change
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DOI：
10.1016/j.cell.2011.05.029
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发表时间：
2011-06-24
期刊：
影响因子：
64.5
通讯作者：
Ishii, Shunsuke
中科院分区：
文献类型：
--
作者：
Seong, Ki-Hyeon;Li, Dong;Ishii, Shunsuke
Atf 1是激活转录因子-2（ATF-2）的裂殖酵母同源物，有助于异染色质的形成。然而，ATF-2在高等生物染色质组装中的作用仍然未知。这项研究表明，果蝇ATF-2（dATF-2）是异染色质组装所必需的，而压力诱导的磷酸化dATF-2，通过Mekk 1-p38，破坏异染色质。dATF-2蛋白与HP 1共定位，不仅在异染色质上，而且在常染色质的特定位点。热休克或渗透胁迫诱导dATF-2磷酸化，并导致其从异染色质中释放。这种异染色质破坏是一种表观遗传事件，以非孟德尔方式传递给下一代。当胚胎在多代中暴露于热应激时，有缺陷的染色质状态在连续多代中保持，尽管它逐渐恢复到正常状态。结果表明，压力的影响是通过调节紧密的染色质结构的表观遗传机制。
Atf1, the fission yeast homolog of activation transcription factor-2 (ATF-2), contributes to heterochromatin formation. However, the role of ATF-2 in chromatin assembly in higher organisms remains unknown. This study reveals that Drosophila ATF-2 (dATF-2) is required for heterochromatin assembly, whereas the stress-induced phosphorylation of dATF-2, via Mekk1-p38, disrupts heterochromatin. The dATF-2 protein colocalized with HP1, not only on heterochromatin but also at specific loci in euchromatin. Heat shock or osmotic stress induced phosphorylation of dATF-2 and resulted in its release from heterochromatin. This heterochromatic disruption was an epigenetic event that was transmitted to the next generation in a non-Mendelian fashion. When embryos were exposed to heat stress over multiple generations, the defective chromatin state was maintained over multiple successive generations, though it gradually returned to the normal state. The results suggest a mechanism by which the effects of stress are inherited epigenetically via the regulation of a tight chromatin structure.