The pronuclei - 20 years later

Abstract

The early mouse embryo is an excellent model to study chromatin changes that underlie zygotic gene activation. Chromatin remodelling in the fertilised mouse egg is intimately linked to protein synthesis and degradation, to protamine by histone replacement and to specific histone modifications. Roumen Tsanev made significant contributions in this field of research. He generated seminal data on pronuclear development and analysed the restoration of transcriptional competence of the inactive gamete chromatin. He identified sperm specific chromatin components, tightly bound to DNA and was one of the first to demonstrate that the histone complement of the male pronucleus appears before the onset of DNA synthesis. In this review we discuss recent genetic data on chromatin remodelling at fertilization. Data from developmentally regulated loci in knock-out mice confirm that first mitosis is associated with a transcriptionally repressive state, gradually relieved by various levels of acetylation and methylation at specific histone motifs. We examine the complexity of the transcriptional revival in the fertilized egg and present results from cutting edge technologies addressing the intricacies of the zygotic genome activation. We illustrate the importance of knowledge about these phenomena for the practical approaches of mammalian cloning and pre-implantation diagnosis. A next step in the field is to correlate the phenotype with the expression profiles of early markers in preimplantation embryos and open the door to see how regulatory pathways interact to underlie pathology reported after routine in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI) protocols. The flurry of exciting data in this hot field of research speaks even better about the creative intuition in Dr. Tsanev's projects that traced a pioneering path in pronuclear biology and genetics. © 2009 Taylor and Francis Group, LLC.