2023-11-10 08:32:08
In the nucleus of cells, DNA is universally associated with histone proteins to form chromatin. This organization of DNA allows different nuclear activities, such as replication, condensation of chromosomes in mitosis or gene expression. However, in many species, male gametes represent an exception: during the long process of sperm formation, histones are replaced by male germline-specific proteins called protamines. Although it is generally accepted that protamines contribute to efficiently compacting DNA in the restricted volume of sperm nuclei, the role of this particular organization of sperm chromatin has never been functionally tested and remains very enigmatic.
Drosophila represents a model of choice for studying this question. The power of fly genetics makes it possible to efficiently identify genes encoding proteins involved in these chromatin remodeling processes. In addition, the different stages of spermatogenesis, and more particularly the histone-protamine transition, are easily observed by confocal microscopy, which generally uses laser as a light source and numerous fluorescent markers. Finally, Drosophila females lay their eggs quickly following fertilization, which makes it easy to study the consequences of a modification in the organization of sperm chromatin on early embryonic development.
Histone removal to protect the epigenetic identity of paternal chromosomes
Thanks to the study of a mutant called paternal loss (pal), isolated in a genetic screen in the early 1970s, scientists unexpectedly discovered that the removal of histones from sperm chromatin is not essential for spermatogenesis but is instead critical for protecting paternal chromosomes following fertilization . Scientists show that in the mutant pal, histones are abnormally retained in the sperm nucleus. These nuclei, which have a characteristic needle shape, are shortened by a third of their length and are also thicker. This change in the morphology of the nuclei has no notable consequences on the ability of sperm to penetrate the egg. However, following fertilization the paternal chromosomes of the mutants pal are abnormally recognized by egg proteins that control the meiotic division of maternal chromosomes. The paternal chromosomes then behave like maternal chromosomes and engage in aberrant meiotic division which leads to the fragmentation of the paternal pronucleus and the loss of chromosomes at the start of embryo development.
This study demonstrates for the first time a fundamental function of the removal of histones from the sperm nucleus in Drosophila: determining and protecting the epigenetic identity of paternal chromosomes following fertilization. This discovery profoundly changes our understanding of the histone-protamine transition which exists in many species, including humans. Finally, the analysis of this remarkable mutant highlights the extraordinary plasticity of sperm chromatin in insects.
© Raphaëlle Dubruille, Benjamin Loppin
Figure: The paternal loss (pal) effect mutant causes fragmentation of the male pronucleus following fertilization. (A) Diagram showing the first stages following fertilization in Drosophila. When the sperm enters the egg, female meiosis then blocked in metaphase of meiosis I resumes. The sperm nucleus decondenses: protamines (green) are replaced by histones (red). After meiosis, the female nucleus migrates and attaches itself to the male nucleus. (B) Microscopy images in an embryo labeled for histones (red), DNA (blue), and Lamin (white), which forms the nuclear envelope. Top: apposition of male and female pronuclei in a control embryo (WT). Bottom: apposition of pronuclei in an egg fertilized by a pal mutant. The paternal nucleus is fragmented.
Learn more:
Histone removal in sperm protects paternal chromosomes from premature division at fertilization. Dubruille R, Herbette M, Revel M, Horard B, Chang CH, Loppin B. Science (2023)
DOI: 10.1126/science.adh0037
1699605493
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