IDH2 and GLUD1 depletion arrests embryonic development through an H4K20me3 epigenetic barrier in porcine parthenogenetic embryosOACSTPCD
Isocitrate dehydrogenase 2(IDH2)and glutamate dehydrogenase 1(GLUD1)are key enzymes involved in the production ofα-ketoglutarate(α-KG),a metabolite central to the tricarboxylic acid cycle and glutamine metabolism.In this study,we investigated the impact of IDH2 and GLUD1 on early porcine embryonic development following IDH2 and GLUD1 knockdown(KD)via doublestranded RNA(dsRNA)microinjection.Results showed that KD reducedα-KG levels,leading to delayed embryonic development,decreased blastocyst formation,increased apoptosis,reduced blastomere proliferation,and pluripotency.Additionally,IDH2 and GLUD1 KD induced abnormally high levels of trimethylation of lysine 20 of histone H4(H4K20me3)at the 4-cell stage,likely resulting in transcriptional repression of embryonic genome activation(EGA)-related genes.Notably,KD of lysine methyltransferase 5C(KMT5C)and supplementation with exogenousα-KG reduced H4K20me3 expression and partially rescued these defects,suggesting a critical role of IDH2 and GLUD1 in the epigenetic regulation and proper development of porcine embryos.Overall,this study highlights the significance of IDH2 and GLUD1 in maintaining normal embryonic development through their influence onα-KG production and subsequent epigenetic modifications.
Cheng-Lin Zhan;Qin-Yue Lu;Song-Hee Lee;Xiao-Han Li;Ji-Dam Kim;Gyu-Hyun Lee;Jae-Min Sim;Hyeon-Ji Song;Ying-Yan Jin;Xiang-Shun Cui
Department of Animal Science,Chungbuk National University,Cheongju,Chungbuk 28644,Republic of KoreaDepartment of Animal Science,Chungbuk National University,Cheongju,Chungbuk 28644,Republic of KoreaDepartment of Animal Science,Chungbuk National University,Cheongju,Chungbuk 28644,Republic of KoreaDepartment of Animal Science,Chungbuk National University,Cheongju,Chungbuk 28644,Republic of KoreaDepartment of Animal Science,Chungbuk National University,Cheongju,Chungbuk 28644,Republic of KoreaDepartment of Animal Science,Chungbuk National University,Cheongju,Chungbuk 28644,Republic of KoreaDepartment of Animal Science,Chungbuk National University,Cheongju,Chungbuk 28644,Republic of KoreaDepartment of Animal Science,Chungbuk National University,Cheongju,Chungbuk 28644,Republic of KoreaDepartment of Animal Science,Chungbuk National University,Cheongju,Chungbuk 28644,Republic of KoreaDepartment of Animal Science,Chungbuk National University,Cheongju,Chungbuk 28644,Republic of Korea
生物学
A-ketoglutarateH4K20me3IDH2GLUD1Embryonic development
《Zoological Research》 2024 (6)
P.1175-1187,13
supported by the National Research Foundation(NRF)of Korea grant funded by the Korean government(MSIT)(2022R1A2C300769),Republic of Korea。
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