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J Biol Chem. 2018 Mar 9;293(10):3829-3838. doi: 10.1074/jbc.RA117.001150. Epub 2018 Jan 22.

Histone variant H3.3-mediated chromatin remodeling is essential for paternal genome activation in mouse preimplantation embryos.

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From the Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine and.
Key Laboratory of Animal Cellular and Genetics Engineering of Heilongjiang Province, College of Life Science, Northeast Agricultural University, Harbin 150030, China, and.
Laboratory of Chromatin Biology and Epigenetics, Rockefeller University, New York, New York 10065.
Department of Medicine, Weill Cornell Medical College, New York, New York 10065.
From the Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine and


Derepression of chromatin-mediated transcriptional repression of paternal and maternal genomes is considered the first major step that initiates zygotic gene expression after fertilization. The histone variant H3.3 is present in both male and female gametes and is thought to be important for remodeling the paternal and maternal genomes for activation during both fertilization and embryogenesis. However, the underlying mechanisms remain poorly understood. Using our H3.3B-HA-tagged mouse model, engineered to report H3.3 expression in live animals and to distinguish different sources of H3.3 protein in embryos, we show here that sperm-derived H3.3 (sH3.3) protein is removed from the sperm genome shortly after fertilization and extruded from the zygotes via the second polar bodies (PBII) during embryogenesis. We also found that the maternal H3.3 (mH3.3) protein is incorporated into the paternal genome as early as 2 h postfertilization and is detectable in the paternal genome until the morula stage. Knockdown of maternal H3.3 resulted in compromised embryonic development both of fertilized embryos and of androgenetic haploid embryos. Furthermore, we report that mH3.3 depletion in oocytes impairs both activation of the Oct4 pluripotency marker gene and global de novo transcription from the paternal genome important for early embryonic development. Our results suggest that H3.3-mediated paternal chromatin remodeling is essential for the development of preimplantation embryos and the activation of the paternal genome during embryogenesis.


chromatin remodeling; development; embryo; embryogenesis; embryonic development; epigenetic reprogramming; epigenetics; fertilization; gene expression; histone; histone variant H3.3; oocyte; paternal genome activation; sperm; transcriptional repression

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