SIRT1 as a key factor for histone code establishment in early embryo, from a perspective of assisted reproduction

Abstract

Both the paternal and the maternal pronuclear chromatin undergo the erasure and re-establishment of epigenetic marks during mammalian zygotic development. These epigenetic changes regulate the totipotency, self-renewal and eventually cell differentiation within the preimplantation embryo. The demethylation of DNA and establishment of adequate post-translational histone modifications, called histone code within the zygote, are required for successful development and reflects the male or female origin of chromatin. Further epigenetic changes are necessary for developmentally regulated transcription and determination of embryonic cell lineage as the embryo blastomeres become transcriptionally active during major zygotic genome activation (MZGA). In addition to DNA methylation, histone code modifications and their regulation are intensively studied. Sirtuin SIRT1, a member of the NADP+ -dependent histone deacetylase family, modifies histones via direct deacetylation as well as indirectly through non-histone substrate regulation. Positive effects of SIRT1 activation on cell viability and embryonic development have been described, and correct histone code modulation is the proposed mode of SIRT1 action. Understanding SIRT1-dependent signalling will provide new tools for assisted reproductive technology in animals and therapy in humans, wherein the inadequate epigenetic modification is a possible explanation for the failure of embryo development in vitro.