TY - JOUR
T1 - Paternal restraint stress affects offspring metabolism via ATF-2 dependent mechanisms in Drosophila melanogaster germ cells
AU - Seong, Ki Hyeon
AU - Ly, Nhung Hong
AU - Katou, Yuki
AU - Yokota, Naoko
AU - Nakato, Ryuichiro
AU - Murakami, Shinnosuke
AU - Hirayama, Akiyoshi
AU - Fukuda, Shinji
AU - Kang, Siu
AU - Soga, Tomoyoshi
AU - Shirahige, Katsuhiko
AU - Ishii, Shunsuke
N1 - Funding Information:
The authors would like to thank Dr Hong Yang and Bloomington stock center for sending stocks and vectors. We thank Yuko Iijima for her technical assistance. We are very grateful to Dr Yoichi Shinkai for helpful support. This work was supported by the AMED (Japan Agency for Medical Research and Development) [18gm0510015h0006 to S.I., JP18gm1110001 to K.-H.S., JP19gm1010009 to S.F.]; MEXT (Ministry of Education, Culture, Sports, Science and Technology) [16H01413 to S.I.]; JST PRESTO (Japan Science and Technology agency, Precursory Research for Embryonic Science and Technology) [JPMJPR12M5 to K.-H.S., JPMJPR1537 to S.F.]; JSPS KAKENHI (Japan Society for the Promotion of Science KAKENHI) [26440192, 19K06497 to K.-H.S., 18H04805 to S.F.]; The Takeda Science Foundation (to S.F.); and The Food Science Institute Foundation (to S.F.).
Publisher Copyright:
© 2020, The Author(s).
PY - 2020/12/1
Y1 - 2020/12/1
N2 - Paternal environmental factors can epigenetically influence gene expressions in offspring. We demonstrate that restraint stress, an experimental model for strong psychological stress, to fathers affects the epigenome, transcriptome, and metabolome of offspring in a MEKK1-dATF2 pathway-dependent manner in Drosophila melanogaster. Genes involved in amino acid metabolism are upregulated by paternal restraint stress, while genes involved in glycolysis and the tricarboxylic acid (TCA) cycle are downregulated. The effects of paternal restraint stress are also confirmed by metabolome analysis. dATF-2 is highly expressed in testicular germ cells, and restraint stress also induces p38 activation in the testes. Restraint stress induces Unpaired 3 (Upd3), a Drosophila homolog of Interleukin 6 (IL-6). Moreover, paternal overexpression of upd3 in somatic cells disrupts heterochromatin in offspring but not in offspring from dATF-2 mutant fathers. These results indicate that paternal restraint stress affects metabolism in offspring via inheritance of dATF-2-dependent epigenetic changes.
AB - Paternal environmental factors can epigenetically influence gene expressions in offspring. We demonstrate that restraint stress, an experimental model for strong psychological stress, to fathers affects the epigenome, transcriptome, and metabolome of offspring in a MEKK1-dATF2 pathway-dependent manner in Drosophila melanogaster. Genes involved in amino acid metabolism are upregulated by paternal restraint stress, while genes involved in glycolysis and the tricarboxylic acid (TCA) cycle are downregulated. The effects of paternal restraint stress are also confirmed by metabolome analysis. dATF-2 is highly expressed in testicular germ cells, and restraint stress also induces p38 activation in the testes. Restraint stress induces Unpaired 3 (Upd3), a Drosophila homolog of Interleukin 6 (IL-6). Moreover, paternal overexpression of upd3 in somatic cells disrupts heterochromatin in offspring but not in offspring from dATF-2 mutant fathers. These results indicate that paternal restraint stress affects metabolism in offspring via inheritance of dATF-2-dependent epigenetic changes.
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U2 - 10.1038/s42003-020-0935-z
DO - 10.1038/s42003-020-0935-z
M3 - Article
C2 - 32367035
AN - SCOPUS:85084234218
VL - 3
JO - Communications Biology
JF - Communications Biology
SN - 2399-3642
IS - 1
M1 - 208
ER -