Distinct dynamics of parental 5-hydroxymethylcytosine during human preimplantation development regulate early lineage gene expression.

Autor: Liang D; Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, Hefei, China. ahmuxl@sina.com., Yan R; Key Laboratory of Organ Regeneration and Reconstruction, State Key Laboratory of Stem Cell and Reproductive Biology, Institute for Stem Cell and Regeneration, Institute of Zoology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Beijing, China.; Beijing Institute for Stem Cell and Regenerative Medicine, Beijing, China., Long X; Key Laboratory of Organ Regeneration and Reconstruction, State Key Laboratory of Stem Cell and Reproductive Biology, Institute for Stem Cell and Regeneration, Institute of Zoology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Beijing, China.; Beijing Institute for Stem Cell and Regenerative Medicine, Beijing, China., Ji D; Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.; NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract, Hefei, China., Song B; Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.; NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract, Hefei, China., Wang M; Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.; NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract, Hefei, China., Zhang F; Key Laboratory of Organ Regeneration and Reconstruction, State Key Laboratory of Stem Cell and Reproductive Biology, Institute for Stem Cell and Regeneration, Institute of Zoology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Beijing, China.; Beijing Institute for Stem Cell and Regenerative Medicine, Beijing, China., Cheng X; Key Laboratory of Organ Regeneration and Reconstruction, State Key Laboratory of Stem Cell and Reproductive Biology, Institute for Stem Cell and Regeneration, Institute of Zoology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Beijing, China.; Beijing Institute for Stem Cell and Regenerative Medicine, Beijing, China., Sun F; Key Laboratory of Organ Regeneration and Reconstruction, State Key Laboratory of Stem Cell and Reproductive Biology, Institute for Stem Cell and Regeneration, Institute of Zoology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Beijing, China.; Beijing Institute for Stem Cell and Regenerative Medicine, Beijing, China., Zhu R; Key Laboratory of Organ Regeneration and Reconstruction, State Key Laboratory of Stem Cell and Reproductive Biology, Institute for Stem Cell and Regeneration, Institute of Zoology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Beijing, China.; Beijing Institute for Stem Cell and Regenerative Medicine, Beijing, China., Hou X; Key Laboratory of Organ Regeneration and Reconstruction, State Key Laboratory of Stem Cell and Reproductive Biology, Institute for Stem Cell and Regeneration, Institute of Zoology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Beijing, China.; Beijing Institute for Stem Cell and Regenerative Medicine, Beijing, China., Wang T; Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.; NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract, Hefei, China., Zou W; Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.; NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract, Hefei, China., Zhang Y; Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.; NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract, Hefei, China., Pu Z; Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.; NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract, Hefei, China., Zhang J; Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.; NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract, Hefei, China., Zhang Z; Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.; NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract, Hefei, China., Liu Y; Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.; NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract, Hefei, China., Hu Y; Key Laboratory of Organ Regeneration and Reconstruction, State Key Laboratory of Stem Cell and Reproductive Biology, Institute for Stem Cell and Regeneration, Institute of Zoology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Beijing, China.; Beijing Institute for Stem Cell and Regenerative Medicine, Beijing, China., He X; NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract, Hefei, China. hxj0117@126.com.; Reproductive Medicine Center, Department of Obstetrics and Gynecology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. hxj0117@126.com., Cao Y; Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, Hefei, China. caoyunxia6@126.com.; NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract, Hefei, China. caoyunxia6@126.com., Guo F; Key Laboratory of Organ Regeneration and Reconstruction, State Key Laboratory of Stem Cell and Reproductive Biology, Institute for Stem Cell and Regeneration, Institute of Zoology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Beijing, China. guofan@ioz.ac.cn.; Beijing Institute for Stem Cell and Regenerative Medicine, Beijing, China. guofan@ioz.ac.cn.
Jazyk: angličtina
Zdroj: Nature cell biology [Nat Cell Biol] 2024 Sep; Vol. 26 (9), pp. 1458-1469. Date of Electronic Publication: 2024 Jul 30.
DOI: 10.1038/s41556-024-01475-y
Abstrakt: The conversion of DNA 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) by TET enzymes represents a significant epigenetic modification, yet its role in early human embryos remains largely unknown. Here we showed that the early human embryo inherited a significant amount of 5hmCs from an oocyte, which unexpectedly underwent de novo hydroxymethylation during its growth. Furthermore, the generation of 5hmC in the paternal genome after fertilization roughly followed the maternal pattern, which was linked to DNA methylation dynamics and regions of sustained methylation. The 5hmCs persisted until the eight-cell stage and exhibited high enrichment at OTX2 binding sites, whereas knockdown of OTX2 in human embryos compromised the expression of early lineage genes. Specifically, the depletion of 5hmC affected the activation of embryonic genes, which was further evaluated by ectopically expressing mouse Tet3 in human early embryos. These findings revealed distinct dynamics of 5hmC and unravelled its multifaceted functions in early human embryonic development.
(© 2024. The Author(s).)
Databáze: MEDLINE
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