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SIRT1-dependent modulation of methylation and acetylation of histone H3 on lysine 9(H3K9)in the zygotic pronuclei improves porcine embryo development

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Journal of Animal Science and Biotechnology 2018年第2期9卷 339-350页

作者： Katerina Adamkova Young-Joo Yi Jaroslav Petr Tereza Zalmanova Kristyna Hoskova Pavla Jelinkova Jiri Moravec Milena Kralickova miriam sutovsky Peter sutovsky Jan Nevoral Department of Veterinary Sciences Faculty of AgricultureFood and Natural ResourcesCzech University of Life Sciences Prague6-SuchdolPragueCzech Republic Division of Biotechnology SafetyEnvironment and Life Science InstituteCollege of Environmental and Bioresource SciencesChonbuk National UniversityIksan 54596South Korea Institute of Animal Science 10-UhrinevesPragueCzech Republic Proteomic Laboratory Biomedical Center of Faculty of Medicine in PilsenCharles UniversityPilsenCzech Republic Laboratory of Reproductive Medicine of Biomedical Center Charles UniversityPilsenCzech Republic Department of Histology and Embryology Faculty of Medicine in PilsenCharles UniversityPilsenCzech Republic Division of Animal Science University of MissouriColumbiaMOUSA Departments of Obstetrics Gynecology and Women’s HealthUniversity of MissouriColumbiaMOUSA

Background: The histone code is an established epigenetic regulator of early embryonic development in *** lysine residue K9 of histone H3(H3 K9) is a prime target of SIRT1, a member of NAD+-dependent histone deacetylase family of enzymes targeting both histone and non-histone substrates. At present, little is known about SIRT1-modulation of H3 K9 in zygotic pronuclei and its association with the success of preimplantation embryo development. Therefore, we evaluated the effect of SIRT1 activity on H3 K9 methylation and acetylation in porcine zygotes and the significance of H3 K9 modifications for early embryonic ***: Our results show that SIRT1 activators resveratrol and BML-278 increased H3 K9 methylation and suppressed H3 K9 acetylation in both the paternal and maternal pronucleus. Inversely, SIRT1 inhibitors nicotinamide and sirtinol suppressed methylation and increased acetylation of pronuclear H3 K9. Evaluation of early embryonic development confirmed positive effect of selective SIRT1 activation on blastocyst formation rate(5.2 ± 2.9% versus 32.9 ± 8.1% in vehicle control and BML-278 group, respectively; P ≤ 0.05). Stimulation of SIRT1 activity coincided with fluorometric signal intensity of ooplasmic ubiquitin ligase MDM2, a known substrate of SIRT1 and known limiting factor of epigenome ***: We conclude that SIRT1 modulates zygotic histone code, obviously through direct deacetylation and via non-histone targets resulting in increased H3 K9 me3. These changes in zygotes lead to more successful pre-implantation embryonic development and, indeed, the specific SIRT1 activation due to BML-278 is beneficial for in vitro embryo production and blastocyst achievement.

关键词： Embryonic development Epigenetics H3K9 methylation SIRT1 Sirtuin

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