Inheritance of stress-induced, ATF-2-dependent epigenetic change.

Ki-Hyeon Seong, Dong Li, Hideyuki Shimizu, Ryoichi Nakamura, Shunsuke Ishii

Laboratory of Molecular Genetics, RIKEN Tsukuba Institute, 3-1-1 Koyadai, Tsukuba, Ibaraki 305-0074, Japan.

Cell 2011 Jun 24

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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. Copyright © 2011 Elsevier Inc. All rights reserved.

Citation

Ki-Hyeon Seong, Dong Li, Hideyuki Shimizu, Ryoichi Nakamura, Shunsuke Ishii. Inheritance of stress-induced, ATF-2-dependent epigenetic change. Cell. 2011 Jun 24;145(7):1049-61