Transient JMJD2B-Mediated Reduction of H3K9me3 Levels Improves Reprogramming of Embryonic Stem Cells into Cloned Embryos

Author:

Antony Jisha1,Oback Fleur1,Chamley Larry W.2,Oback Björn1,Laible Götz1

Affiliation:

1. AgResearch Ruakura Research Centre, Hamilton, New Zealand

2. Department of Obstetrics and Gynaecology, University of Auckland, Auckland, New Zealand

Abstract

ABSTRACT Correct reprogramming of epigenetic marks in the donor nuclei is crucial for successful cloning by nuclear transfer. Specific epigenetic modifications, such as repressive histone lysine methylation marks, are known to be very stable and difficult to reprogram. The discovery of histone lysine demethylases has opened up opportunities to study the effects of removing repressive histone lysine methylation marks in donor cells prior to nuclear transfer. In this study, we generated mouse embryonic stem (ES) cells for the inducible expression of JMJD2B (also known as KDM4B), a demethylase that primarily removes the histone-3 lysine-9 trimethylation (H3K9me3) mark. Induction of jmjd2b in the ES cells decreased total levels of H3K9me3 by 63%. When these cells were used for nuclear transfer, H3K9me3 levels were normalized within minutes following fusion with an enucleated oocyte. This transient reduction of H3K9me3 levels improved in vitro development into cloned embryos by 30%.

Publisher

American Society for Microbiology

Subject

Cell Biology,Molecular Biology

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