ATF7-dependent epigenetic changes induced by high temperature during early porcine embryonic development

猪早期胚胎发育过程中高温诱导的ATF7依赖性表观遗传变化

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作者:Ming-Hong Sun, Wen-Jie Jiang, Xiao-Han Li, Song-Hee Lee, Geun Heo, Dongjie Zhou, Jung-Seok Choi, Kwan-Suk Kim, Wenfa Lv, Xiang-Shun Cui

Background

Activating transcription factor 7 (ATF7) is a member of the ATF/cAMP response element (CRE) B superfamily. ATF2, ATF7, and CRE-BPa are present in vertebrates. Drosophila and fission yeast have only one homologue: dATF2 and Atf1, respectively. Under normal conditions, ATF7 promotes heterochromatin formation by recruiting histone H3K9 di- and tri-methyltransferases. Once the situation changes, all members are phosphorylated by the stress-activated kinase P38 in response to various stressors. However, the role of ATF7 in early porcine embryonic development remains unclear.

Conclusion

Stress-induced ATF7-dependent epigenetic changes play important roles in early porcine embryonic development.

Results

In this study, we found that ATF7 gradually accumulated in the nucleus and then localized on the pericentric heterochromatin after the late 4-cell stage, while being co-localized with heterochromatin protein 1 (HP1). Knockdown of ATF7 resulted in decreases in the blastocyst rate and blastocyst cell number. ATF7 depletion resulted in downregulation of HP1 and histone 3 lysine 9 dimethylation (H3K9me2) expression. These effects were alleviated when P38 activity was inhibited. High temperatures increased the expression level of pP38, while reducing the quality of porcine embryos, and led to ATF7 phosphorylation. The expression level of H3K9me2 and HP1 was decreased and regulated by P38 activity.

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