PMID- 29358330 OWN - NLM STAT- MEDLINE DCOM- 20190107 LR - 20210205 IS - 1083-351X (Electronic) IS - 0021-9258 (Print) IS - 0021-9258 (Linking) VI - 293 IP - 10 DP - 2018 Mar 9 TI - Histone variant H3.3-mediated chromatin remodeling is essential for paternal genome activation in mouse preimplantation embryos. PG - 3829-3838 LID - 10.1074/jbc.RA117.001150 [doi] AB - 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. CI - (c) 2018 by The American Society for Biochemistry and Molecular Biology, Inc. FAU - Kong, Qingran AU - Kong Q AD - From the Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine and. AD - Key Laboratory of Animal Cellular and Genetics Engineering of Heilongjiang Province, College of Life Science, Northeast Agricultural University, Harbin 150030, China, and. FAU - Banaszynski, Laura A AU - Banaszynski LA AD - Laboratory of Chromatin Biology and Epigenetics, Rockefeller University, New York, New York 10065. FAU - Geng, Fuqiang AU - Geng F AD - Department of Medicine, Weill Cornell Medical College, New York, New York 10065. FAU - Zhang, Xiaolei AU - Zhang X AD - Key Laboratory of Animal Cellular and Genetics Engineering of Heilongjiang Province, College of Life Science, Northeast Agricultural University, Harbin 150030, China, and. FAU - Zhang, Jiaming AU - Zhang J AD - Key Laboratory of Animal Cellular and Genetics Engineering of Heilongjiang Province, College of Life Science, Northeast Agricultural University, Harbin 150030, China, and. FAU - Zhang, Heng AU - Zhang H AD - Key Laboratory of Animal Cellular and Genetics Engineering of Heilongjiang Province, College of Life Science, Northeast Agricultural University, Harbin 150030, China, and. FAU - O'Neill, Claire L AU - O'Neill CL AD - From the Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine and. FAU - Yan, Peidong AU - Yan P AD - Key Laboratory of Animal Cellular and Genetics Engineering of Heilongjiang Province, College of Life Science, Northeast Agricultural University, Harbin 150030, China, and. FAU - Liu, Zhonghua AU - Liu Z AD - Key Laboratory of Animal Cellular and Genetics Engineering of Heilongjiang Province, College of Life Science, Northeast Agricultural University, Harbin 150030, China, and. FAU - Shido, Koji AU - Shido K AD - Department of Medicine, Weill Cornell Medical College, New York, New York 10065. FAU - Palermo, Gianpiero D AU - Palermo GD AD - From the Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine and. FAU - Allis, C David AU - Allis CD AD - Laboratory of Chromatin Biology and Epigenetics, Rockefeller University, New York, New York 10065. FAU - Rafii, Shahin AU - Rafii S AD - Department of Medicine, Weill Cornell Medical College, New York, New York 10065. FAU - Rosenwaks, Zev AU - Rosenwaks Z AD - From the Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine and. FAU - Wen, Duancheng AU - Wen D AD - From the Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine and duw2001@med.cornell.edu. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180122 PL - United States TA - J Biol Chem JT - The Journal of biological chemistry JID - 2985121R RN - 0 (Histones) RN - 0 (Octamer Transcription Factor-3) RN - 0 (Pou5f1 protein, mouse) RN - 0 (Protein Isoforms) RN - 0 (Recombinant Fusion Proteins) RN - 147336-22-9 (Green Fluorescent Proteins) SB - IM MH - Animals MH - Blastocyst/cytology/*metabolism MH - Blastomeres/cytology/metabolism MH - *Chromatin Assembly and Disassembly MH - Embryonic Development MH - Female MH - Gene Expression Regulation, Developmental MH - Green Fluorescent Proteins/genetics/metabolism MH - Histones/antagonists & inhibitors/genetics/*metabolism MH - Male MH - Mice MH - Mice, Inbred ICR MH - Mice, Transgenic MH - Morula/cytology/metabolism MH - Octamer Transcription Factor-3/chemistry/genetics/metabolism MH - *Paternal Inheritance MH - Protein Isoforms/antagonists & inhibitors/genetics/metabolism MH - RNA Interference MH - Recombinant Fusion Proteins/chemistry/metabolism MH - *Transcriptional Activation PMC - PMC5846143 OTO - NOTNLM OT - chromatin remodeling OT - development OT - embryo OT - embryogenesis OT - embryonic development OT - epigenetic reprogramming OT - epigenetics OT - fertilization OT - gene expression OT - histone OT - histone variant H3.3 OT - oocyte OT - paternal genome activation OT - sperm OT - transcriptional repression COIS- The authors declare that they have no conflicts of interest with the contents of this article EDAT- 2018/01/24 06:00 MHDA- 2019/01/08 06:00 PMCR- 2019/03/09 CRDT- 2018/01/24 06:00 PHST- 2017/11/28 00:00 [received] PHST- 2018/01/02 00:00 [revised] PHST- 2018/01/24 06:00 [pubmed] PHST- 2019/01/08 06:00 [medline] PHST- 2018/01/24 06:00 [entrez] PHST- 2019/03/09 00:00 [pmc-release] AID - S0021-9258(20)40420-X [pii] AID - RA117.001150 [pii] AID - 10.1074/jbc.RA117.001150 [doi] PST - ppublish SO - J Biol Chem. 2018 Mar 9;293(10):3829-3838. doi: 10.1074/jbc.RA117.001150. Epub 2018 Jan 22.