TY - JOUR
T1 - Histone variant H3.3–mediated chromatin remodeling is essential for paternal genome activation in mouse preimplantation embryos
AU - Kong, Qingran
AU - Banaszynski, Laura A.
AU - Geng, Fuqiang
AU - Zhang, Xiaolei
AU - Zhang, Jiaming
AU - Zhang, Heng
AU - O’Neill, Claire L.
AU - Yan, Peidong
AU - Liu, Zhonghua
AU - Shido, Koji
AU - Palermo, Gianpiero D.
AU - David Allis, C.
AU - Rafii, Shahin
AU - Rosenwaks, Zev
AU - Wen, Duancheng
N1 - Funding Information:
This work was supported in part by a Starr Foundation Tri-Institutional Stem Cell Core and Derivation grant (to D. W., Z. R., and S. R.), the National Key Research and Development program of China-Stem cell and Translational Research Grant 2016YFA0100200 (to Q. K. and Z. L.), and “Academic Back-bone” Project of Northeast Agricultural University Grant 15XG19 (to Q. K. and Z. L.). The authors declare that they have no conflicts of interest with the contents of this article.
Funding Information:
1 Supported by China Scholarship Council Grant 201606615019.
PY - 2018/3/9
Y1 - 2018/3/9
N2 - 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.
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.
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U2 - 10.1074/jbc.RA117.001150
DO - 10.1074/jbc.RA117.001150
M3 - Article
C2 - 29358330
AN - SCOPUS:85043578129
VL - 293
SP - 3829
EP - 3838
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 10
ER -