Active H3K27me3 demethylation by KDM6B is required for normal development of bovine preimplantation embryos

The substantial epigenetic remodeling that occurs during early stages of mammalian embryonic development likely contributes to reprogramming the parental genomes from a differentiated to a totipotent state and activation of the embryonic genome. Trimethylation of lysine 27 of histone 3 (H3K27me3) is...

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Main Authors: Nhi Chung, Yanina S. Bogliotti, Wei Ding, Marcela Vilarino, Kazuki Takahashi, James L. Chitwood, Richard M. Schultz, Pablo J. Ross
Format: Article
Language:English
Published: Taylor & Francis Group 2017-12-01
Series:Epigenetics
Subjects:
Online Access:http://dx.doi.org/10.1080/15592294.2017.1403693
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author Nhi Chung
Yanina S. Bogliotti
Wei Ding
Marcela Vilarino
Kazuki Takahashi
James L. Chitwood
Richard M. Schultz
Pablo J. Ross
author_facet Nhi Chung
Yanina S. Bogliotti
Wei Ding
Marcela Vilarino
Kazuki Takahashi
James L. Chitwood
Richard M. Schultz
Pablo J. Ross
author_sort Nhi Chung
collection DOAJ
description The substantial epigenetic remodeling that occurs during early stages of mammalian embryonic development likely contributes to reprogramming the parental genomes from a differentiated to a totipotent state and activation of the embryonic genome. Trimethylation of lysine 27 of histone 3 (H3K27me3) is a repressive mark that undergoes global dynamic changes during preimplantation development of several species. To ascertain the role of H3K27me3 in bovine preimplantation development we perturbed the activity of KDM6B, which demethylates H3K27me3. Knockdown of maternal KDM6B mRNA inhibited the reduction in global levels of H3K27me3 from 2-cell to 8-cell embryo stages and compromised development to the blastocyst stage; embryos that developed to the blastocyst stage had fewer inner cell mass (ICM) and trophectoderm (TE) cells. In addition, the transcriptome of KDM6B knockdown embryos was altered at the 8-cell stage and characterized by downregulation of transcripts related to transcriptional regulation, chromatin remodeling, and protein catabolism. Inhibiting the catalytic activity of KDM6B with a specific small molecule inhibitor also prevented the global decrease in H3K27me3 and compromised development to the blastocyst stage. These results indicate that histone demethylation activity, mediated by KDM6B, is required for the global decrease in H3K27me3, correct activation of the embryonic genome, and development to the blastocyst stage in bovine embryos.
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spelling doaj.art-f731d54c5203461e901b7f7a3c0462db2023-09-21T13:09:20ZengTaylor & Francis GroupEpigenetics1559-22941559-23082017-12-0112121048105610.1080/15592294.2017.14036931403693Active H3K27me3 demethylation by KDM6B is required for normal development of bovine preimplantation embryosNhi Chung0Yanina S. Bogliotti1Wei Ding2Marcela Vilarino3Kazuki Takahashi4James L. Chitwood5Richard M. Schultz6Pablo J. Ross7University of California DavisUniversity of California DavisUniversity of California DavisUniversity of California DavisUniversity of California DavisUniversity of California DavisUniversity of California DavisUniversity of California DavisThe substantial epigenetic remodeling that occurs during early stages of mammalian embryonic development likely contributes to reprogramming the parental genomes from a differentiated to a totipotent state and activation of the embryonic genome. Trimethylation of lysine 27 of histone 3 (H3K27me3) is a repressive mark that undergoes global dynamic changes during preimplantation development of several species. To ascertain the role of H3K27me3 in bovine preimplantation development we perturbed the activity of KDM6B, which demethylates H3K27me3. Knockdown of maternal KDM6B mRNA inhibited the reduction in global levels of H3K27me3 from 2-cell to 8-cell embryo stages and compromised development to the blastocyst stage; embryos that developed to the blastocyst stage had fewer inner cell mass (ICM) and trophectoderm (TE) cells. In addition, the transcriptome of KDM6B knockdown embryos was altered at the 8-cell stage and characterized by downregulation of transcripts related to transcriptional regulation, chromatin remodeling, and protein catabolism. Inhibiting the catalytic activity of KDM6B with a specific small molecule inhibitor also prevented the global decrease in H3K27me3 and compromised development to the blastocyst stage. These results indicate that histone demethylation activity, mediated by KDM6B, is required for the global decrease in H3K27me3, correct activation of the embryonic genome, and development to the blastocyst stage in bovine embryos.http://dx.doi.org/10.1080/15592294.2017.1403693cattleembryonic genome activationh3k27me3histone demethylationjmjd3preimplantation developmentreprogrammingtotipotency
spellingShingle Nhi Chung
Yanina S. Bogliotti
Wei Ding
Marcela Vilarino
Kazuki Takahashi
James L. Chitwood
Richard M. Schultz
Pablo J. Ross
Active H3K27me3 demethylation by KDM6B is required for normal development of bovine preimplantation embryos
Epigenetics
cattle
embryonic genome activation
h3k27me3
histone demethylation
jmjd3
preimplantation development
reprogramming
totipotency
title Active H3K27me3 demethylation by KDM6B is required for normal development of bovine preimplantation embryos
title_full Active H3K27me3 demethylation by KDM6B is required for normal development of bovine preimplantation embryos
title_fullStr Active H3K27me3 demethylation by KDM6B is required for normal development of bovine preimplantation embryos
title_full_unstemmed Active H3K27me3 demethylation by KDM6B is required for normal development of bovine preimplantation embryos
title_short Active H3K27me3 demethylation by KDM6B is required for normal development of bovine preimplantation embryos
title_sort active h3k27me3 demethylation by kdm6b is required for normal development of bovine preimplantation embryos
topic cattle
embryonic genome activation
h3k27me3
histone demethylation
jmjd3
preimplantation development
reprogramming
totipotency
url http://dx.doi.org/10.1080/15592294.2017.1403693
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