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14 July 2022 Ten-Eleven Translocation-3 CXXC domain is critical for postfertilization demethylation and expression of pluripotency genes in pig embryos
Kyungjun Uh, Kiho Lee
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Enzymes of the ten-eleven translocation family are considered to play an important role in the regulation of DNA methylation patterns by converting 5-methylcytosine to 5-hydroxymethylcytosine. Known as a maternal transcript enriched in mature oocytes, ten-eleven translocation-3 (TET3) has been suggested to initiate DNA demethylation of the paternal genome in zygotes. Previous studies in mouse cells indicate that the N-terminal CXXC domain of TET3 is important in catalyzing the oxidation of 5-methylcytosine through its potential DNA binding ability; however, it is not clear whether the DNA binding capacity of CXXC domain is required for the 5-hydroxymethylcytosine conversion in mammalian embryos. Here, we identified TET3 isoforms in porcine oocytes and investigated the role of the oocyte specific TET3 isoform (pTET3L) in controlling postfertilization demethylation in porcine embryos. The pTET3L possessed sequences representing a known DNA binding domain, the CXXC, and injection of the TET3 CXXC fused with GFP into mature porcine oocytes resulted in exclusive localization of the GFP-CXXC in the pronuclei. The CXXC overexpression reduced the 5-methylcytosine level in zygotes and enhanced the DNA demethylation of the NANOG promoter in 2-cell stage embryos. Furthermore, there was an increase in the transcript abundance of NANOG and ESRRB in blastocysts developed from GFP-CXXC injected oocytes. Targeted knockdown of pTET3L resulted in the downregulation of pluripotency genes in subsequently developed blastocysts. The findings indicate that the CXXC domain of TET3 serves as a critical component for the postfertilization demethylation of porcine embryos and coordinates proper expression of pluripotency related genes in blastocysts.

Summary Sentence

TET3 isoform containing CXXC domain is the predominant isoform in porcine oocytes and orchestrates postfertilization demethylation and proper expression of pluripotency genes in porcine embryos.

© The Author(s) 2022. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail:
Kyungjun Uh and Kiho Lee "Ten-Eleven Translocation-3 CXXC domain is critical for postfertilization demethylation and expression of pluripotency genes in pig embryos," Biology of Reproduction 107(5), 1205-1216, (14 July 2022).
Received: 16 February 2022; Accepted: 18 June 2022; Published: 14 July 2022
DNA methylation
epigenetic reprogramming
porcine embryo
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