The Essential Role of Drosophila HIRA for De Novo Assembly of Paternal Chromatin at Fertilization

European Molecular Biology Laboratory, Germany
PLoS Genetics (Impact Factor: 7.53). 11/2007; 3(10):1991-2006. DOI: 10.1371/journal.pgen.0030182
Source: PubMed


In many animal species, the sperm DNA is packaged with male germ line--specific chromosomal proteins, including protamines. At fertilization, these non-histone proteins are removed from the decondensing sperm nucleus and replaced with maternally provided histones to form the DNA replication competent male pronucleus. By studying a point mutant allele of the Drosophila Hira gene, we previously showed that HIRA, a conserved replication-independent chromatin assembly factor, was essential for the assembly of paternal chromatin at fertilization. HIRA permits the specific assembly of nucleosomes containing the histone H3.3 variant on the decondensing male pronucleus. We report here the analysis of a new mutant allele of Drosophila Hira that was generated by homologous recombination. Surprisingly, phenotypic analysis of this loss of function allele revealed that the only essential function of HIRA is the assembly of paternal chromatin during male pronucleus formation. This HIRA-dependent assembly of H3.3 nucleosomes on paternal DNA does not require the histone chaperone ASF1. Moreover, analysis of this mutant established that protamines are correctly removed at fertilization in the absence of HIRA, thus demonstrating that protamine removal and histone deposition are two functionally distinct processes. Finally, we showed that H3.3 deposition is apparently not affected in Hira mutant embryos and adults, suggesting that different chromatin assembly machineries could deposit this histone variant.

    • "For example, the Histone Cell Cycle Regulation Defective Homolog A (Hira) and Yemanuclein (Yem) genes in the Drosophila are required to package histone H3 (H3.3) to the paternal genome. Loss of HIRA or YEM leads to an irregular paternal pronucleus and the subsequent loss of the paternal genome (Bonnefoy et al., 2007; Orsi et al., 2013). Fertilization is then followed by the process of embryo blastogenesis, the early stages of embryogenesis that is marked by formation of the blastula. "
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    • "In C. elegans zygotes, as in mammals, there are significant alterations to the genome structure, again most strikingly in the sperm chromatin, which rapidly decondenses after fertilization and prior to pronuclear fusion in many organisms [14]. Sperm decondensation is accompanied by incorporation of the histone H3 variant, histone H3.3, which is maternally provided and can become enriched in the sperm pronuclear chromatin relative to that of the oocyte [14-16]. There are also initial differences in a number of histone modifications between the male and female pronuclei prior to fusion in both mammals and C. elegans[14,15] (WK, unpublished work). "
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    • "In C. elegans, D. melanogaster, and mouse, H3.3 of maternal origin is globally deposited in the paternal chromatin upon fertilization, before the first round of replication and onset of detectable zygotic transcription (Loppin et al. 2005, Ooi et al. 2006, Torres-Padilla et al. 2006, van der Heijden et al. 2005). In D. melanogaster, H3.3 incorporation on decondensing sperm is the only developmental process impaired by the loss of HIRA (Bonnefoy et al. 2007). Both the remodeling factor chromodomain helicase DNA-binding protein 1 (CHD1), which associates with HIRA in vivo (Konev et al. 2007), and yemanuclein-α (Table 1) have a contributing role (Orsi et al. 2013). "
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