The Lid/KDM5 histone demethylase complex activates a critical effector of the oocyte-to-zygote transition.

Daniela Torres-Campana,Béatrice Horard,Benjamin Loppin,Guillermo A. Orsi,Shuhei Kimura,Gérard Benoit,Giovanni Bosco

doi:10.1371/journal.pgen.1008543

Abstract

Following fertilization of a mature oocyte, the formation of a diploid zygote involves a series of coordinated cellular events that ends with the first embryonic mitosis. In animals, this complex developmental transition is almost entirely controlled by maternal gene products. How such a crucial transcriptional program is established during oogenesis remains poorly understood. Here, we have performed an shRNA-based genetic screen in Drosophila to identify genes required to form a diploid zygote. We found that the Lid/KDM5 histone demethylase and its partner, the Sin3A-HDAC1 deacetylase complex, are necessary for sperm nuclear decompaction and karyogamy. Surprisingly, transcriptomic analyses revealed that these histone modifiers are required for the massive transcriptional activation of deadhead (dhd), which encodes a maternal thioredoxin involved in sperm chromatin remodeling. Unexpectedly, while lid knock-down tends to slightly favor the accumulation of its target, H3K4me3, on the genome, this mark was lost at the dhd locus. We propose that Lid/KDM5 and Sin3A cooperate to establish a local chromatin environment facilitating the unusually high expression of dhd, a key effector of the oocyte-to-zygote transition.

Highlights

In sexually reproducing animals, fertilization allows the formation of a diploid zygote through the association of two haploid gametes of highly different origins and structures
Male pronucleus formation begins with the genome-wide replacement of Sperm Nuclear Basic Proteins (SNBPs) with maternally supplied histones, a process called sperm chromatin remodeling, which is followed by extensive pronuclear decondensation [1]
We demonstrate that germline knock-down of these histone modifiers prevent sperm chromatin remodeling through a mechanism that depends on the DHD thioredoxin

Summary

Introduction

Fertilization allows the formation of a diploid zygote through the association of two haploid gametes of highly different origins and structures. The spermatozoon delivers its compact nucleus within the egg cytoplasm, along with a pair of centrioles, while the egg provides one haploid meiotic product and all resources to sustain zygote formation [1]. In some species, this maternal control extends to early embryo development, as in Drosophila melanogaster, where the initial amplification of embryo cleavage nuclei occurs without significant zygotic transcription [2]. Male pronucleus formation begins with the genome-wide replacement of SNBPs with maternally supplied histones, a process called sperm chromatin remodeling, which is followed by extensive pronuclear decondensation [1]. Zygote formation involves the coordinated migration and apposition of male and female pronuclei and the switch from meiotic to mitotic division within the same cytoplasm

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Conclusion