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

Qingran Kong, Laura A. Banaszynski, Fuqiang Geng, Xiaolei Zhang, Jiaming Zhang, Heng Zhang, Claire L. O’Neill, Peidong Yan, Zhonghua Liu, Koji Shido, Gianpiero D. Palermo, C. David Allis, Shahin Rafii, Zev Rosenwaks, Duancheng Wen

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)3829-3838
Number of pages10
JournalJournal of Biological Chemistry
Volume293
Issue number10
DOIs
StatePublished - Jan 1 2018

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Chromatin Assembly and Disassembly
Blastocyst
Histones
Chromatin
Embryonic Development
Genes
Chemical activation
Genome
Mothers
Fertilization
Embryonic Structures
Spermatozoa
Polar Bodies
Morula
Proteins
Zygote
Haploidy
Germ Cells
Transcription
Oocytes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Histone variant H3.3–mediated chromatin remodeling is essential for paternal genome activation in mouse preimplantation embryos. / Kong, Qingran; Banaszynski, Laura A.; Geng, Fuqiang; Zhang, Xiaolei; Zhang, Jiaming; Zhang, Heng; O’Neill, Claire L.; Yan, Peidong; Liu, Zhonghua; Shido, Koji; Palermo, Gianpiero D.; David Allis, C.; Rafii, Shahin; Rosenwaks, Zev; Wen, Duancheng.

In: Journal of Biological Chemistry, Vol. 293, No. 10, 01.01.2018, p. 3829-3838.

Research output: Contribution to journalArticle

Kong, Q, Banaszynski, LA, Geng, F, Zhang, X, Zhang, J, Zhang, H, O’Neill, CL, Yan, P, Liu, Z, Shido, K, Palermo, GD, David Allis, C, Rafii, S, Rosenwaks, Z & Wen, D 2018, 'Histone variant H3.3–mediated chromatin remodeling is essential for paternal genome activation in mouse preimplantation embryos', Journal of Biological Chemistry, vol. 293, no. 10, pp. 3829-3838. https://doi.org/10.1074/jbc.RA117.001150
Kong, Qingran ; Banaszynski, Laura A. ; Geng, Fuqiang ; Zhang, Xiaolei ; Zhang, Jiaming ; Zhang, Heng ; O’Neill, Claire L. ; Yan, Peidong ; Liu, Zhonghua ; Shido, Koji ; Palermo, Gianpiero D. ; David Allis, C. ; Rafii, Shahin ; Rosenwaks, Zev ; Wen, Duancheng. / Histone variant H3.3–mediated chromatin remodeling is essential for paternal genome activation in mouse preimplantation embryos. In: Journal of Biological Chemistry. 2018 ; Vol. 293, No. 10. pp. 3829-3838.
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