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Incidence of methylated histones H3K4 and H3K79 in cat germinal vesicles is regulated by specific nuclear factors at the acquisition of developmental competence during the folliculogenesis

  • Gamete Biology
  • Published:
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Abstract

Purpose

This study aims to characterize the regulations of histone methylations, key epigenetic markers of oocyte competence, in germinal vesicle (GV) from different follicles (preantral, early, small, or large antral stage) using the domestic cat model.

Methods

In Experiment 1, the incidence of H3K4me3 or H3K79me2 was determined in GVs from the diverse follicle stages directly or after exposure to (1) a methyltransferase inhibitor, (2) sonication to fracture the cytoplasmic membranes and wash away the cytoplasmic content, or (3) methyltransferase inhibitor followed by sonication. In Experiment 2, the presence and maintenance of nuclear methyltransferases SMYD3 and DOT1L (regulating H3K4me3 and H3K79me2, respectively) was characterized in separate GV stages before and after sonication. Functionality of GVs from the various follicle stages (with or without transient isolation from the cytoplasm) then was assessed in Experiment 3 by transfer into recipient competent oocytes.

Results

The incidence of histones H3K4me3 and H3K79me2 within the GV were influenced by the cytoplasmic environment at all stages except at the transition to the early antral stage where nuclear regulating factors appeared to be mainly involved. The methyltransferase SMYD3 and DOT1L also appeared tightly bound to the nucleus at that transition. Interestingly, oocytes reconstructed with a GV isolated from the cytoplasm for a prolonged period had the capacity to form an embryo after fertilization which proved that communication between the donor GV and the host cytoplasm (likely including the regulation of epigenetic factors) could be restored.

Conclusions

Histone methylation apparently becomes regulated by specific nuclear factors at the acquisition of competence during the folliculogenesis and does not seem to be disrupted by prolonged isolation from the surrounding cytoplasm.

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Acknowledgments

This project was funded by the National Center for Research Resources (R01 R026064), a component of the National Institutes of Health (NIH) and is currently supported by the Office of Research Infrastructure Programs/Office of the Director (R01 OD 010948). No conflict of interests to be declared. We thank Dr. Brent Whitaker (Maryland Line Animal Rescue) for providing domestic cat ovaries.

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Authors and Affiliations

  1. Smithsonian Conservation Biology Institute, National Zoological Park, Washington, DC, 20008, USA

    Tameka C. Phillips, David E. Wildt & Pierre Comizzoli

  2. Smithsonian Conservation Biology Institute, National Zoological Park, Front Royal, VA, 22630, USA

    Tameka C. Phillips, David E. Wildt & Pierre Comizzoli

Authors
  1. Tameka C. Phillips
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  2. David E. Wildt
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  3. Pierre Comizzoli
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Correspondence to Pierre Comizzoli.

Additional information

Capsule Using the domestic cat model, the incidence and regulation of histone methylations in germinal vesicles during folliculogenesis was studied showing that specific nuclear remodeling events occur during the preantral–antral transition when developmental competence is acquired.

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Phillips, T.C., Wildt, D.E. & Comizzoli, P. Incidence of methylated histones H3K4 and H3K79 in cat germinal vesicles is regulated by specific nuclear factors at the acquisition of developmental competence during the folliculogenesis. J Assist Reprod Genet 33, 783–794 (2016). https://doi.org/10.1007/s10815-016-0706-4

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  • DOI: https://doi.org/10.1007/s10815-016-0706-4

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