IDH2 and GLUD1 Depletion Arrests Embryonic Development Through an H4K20me3 Epigenetic Barrier in Porcine Parthenogenetic Embryos

Overview

Journal Zool Res

Publisher Science Press

Specialties Biology
Veterinary Medicine

Date 2024 Sep 25

PMID 39318125

Authors

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

Affiliations

Soon will be listed here.

Abstract

Isocitrate dehydrogenase 2 (IDH2) and glutamate dehydrogenase 1 (GLUD1) are key enzymes involved in the production of α-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 and knockdown (KD) via double-stranded RNA (dsRNA) microinjection. Results showed that KD reduced α-KG levels, leading to delayed embryonic development, decreased blastocyst formation, increased apoptosis, reduced blastomere proliferation, and pluripotency. Additionally, and 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 ( ) and supplementation with exogenous α-KG reduced H4K20me3 expression and partially rescued these defects, suggesting a critical role of and in the epigenetic regulation and proper development of porcine embryos. Overall, this study highlights the significance of and in maintaining normal embryonic development through their influence on α-KG production and subsequent epigenetic modifications.

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