Journal Article

Maternally inherited piRNAs direct transient heterochromatin formation at active transposons during early Drosophila embryogenesis

Fabry, Martin H, Lythgoe, Emily K, Czech, Benjamin, Hannon, Gregory J, Falconio, Federica A, Joud, Fadwa

2021

Overview

The PIWI-interacting RNA (piRNA) pathway controls transposon expression in animal germ cells, thereby ensuring genome stability over generations. In Drosophila , piRNAs are intergenerationally inherited through the maternal lineage, and this has demonstrated importance in the specification of piRNA source loci and in silencing of I- and P- elements in the germ cells of daughters. Maternally inherited Piwi protein enters somatic nuclei in early embryos prior to zygotic genome activation and persists therein for roughly half of the time required to complete embryonic development. To investigate the role of the piRNA pathway in the embryonic soma, we created a conditionally unstable Piwi protein. This enabled maternally deposited Piwi to be cleared from newly laid embryos within 30 min and well ahead of the activation of zygotic transcription. Examination of RNA and protein profiles over time, and correlation with patterns of H3K9me3 deposition, suggests a role for maternally deposited Piwi in attenuating zygotic transposon expression in somatic cells of the developing embryo. In particular, robust deposition of piRNAs targeting roo , an element whose expression is mainly restricted to embryonic development, results in the deposition of transient heterochromatic marks at active roo insertions. We hypothesize that roo , an extremely successful mobile element, may have adopted a lifestyle of expression in the embryonic soma to evade silencing in germ cells. Maintaining the integrity of DNA, which encodes all of the instructions necessary for life, is essential for ensuring the survival of a species, especially when genetic information is transferred across generations. DNA, however, contains selfish, mobile elements, called transposons, that move around the genome, hence their nickname ‘jumping genes’. Their movement, a process by which these elements also multiply within genomes, can muddle an organism’s DNA if the transposon happens to land in the middle of a gene, creating a mutation which renders the gene inactive. Transposons have also been linked to the development of cancer, which is a group of diseases driven by accumulating genetic mutations. Animals have evolved various ways of protecting their DNA against transposons. These are especially important in developing egg cells and sperm, known collectively as germ cells. These cells can produce small fragments of RNA, a molecule similar to DNA, which are able to identify and disarm transposons. While it is known that these small RNAs effectively protect adult gonads from DNA damage, it has been unclear how germ cells formed during the beginning of life are protected. To find out more, Fabry et al. used a combination of genetic sequencing, protein binding and imaging studies to look at the activity of small RNAs, called piRNAs, which are passed on from the mother to her progeny. By studying the gene expression levels in fruit fly embryos, Fabry et al. showed that certain transposons become highly active in the first few hours of embryo development, posing a potential threat to DNA integrity. The experiments also identified clear signs in the embryos of an active mechanism for controlling transposons that resembles the small RNA system known from adult germ cells. Fabry et al. removed the piRNAs from the embryos and found that without piRNAs, transposons were more active. This indicates a direct role of these small RNAs in controlling transposons in early development and evidence for a maternally inherited defence system in early embryos. This study provides insights into the control of transposons in fly embryos. More research is needed to find out whether these embryonic mechanisms are conserved in other animals, including humans. Studying the intrinsic mechanisms that prevent DNA damage and protect our genome could, in time, help to identify new approaches to possibly treat and prevent diseases involving genetic mutations.

• Publisher: eLife Science Publications, Ltd,eLife Sciences Publications Ltd,eLife Sciences Publications, Ltd
• Subject: Animals / Chromatin / Chromosomes and Gene Expression / Developmental Biology / DNA Transposable Elements / Drosophila / Drosophila - embryology / Drosophila - genetics / Drosophila melanogaster - genetics / Drosophila melanogaster - physiology / Drosophila Proteins - metabolism / Embryogenesis / Embryonic development / Embryonic Development - genetics / Embryonic Development - physiology / Embryos / Epigenetics / Epigenomics / Female / Fruit-flies / Gene Expression / Gene mutations / Genes / Genetic aspects / Genetic transcription / Genomes / Genomics / Germ cells / Germ Cells - metabolism / Heterochromatin / Heterochromatin - metabolism / Histones - metabolism / Insects / Male / Mass spectrometry / Maternal Inheritance - genetics / Maternal Inheritance - physiology / Microscopy / Mutation / Ovaries / piRNA pathway / Protein binding / Proteins / RNA / RNA, Small Interfering - metabolism / Scientific equipment and supplies industry / Scientific imaging / Somatic cells / Standard deviation / Transcription activation / transposable elements / Transposons