Biology subjects

Delmarre, V.

Publications and source records attributed to Delmarre, V..

2 recordsLinked to original sources

bioRxiv2022

The histone demethylase KDM3 prevents auto-immune piRNAs production in Drosophila

In animals, genome integrity of the germ line is protected from transposable element (TE) activity by small, non-coding, dedicated RNAs acting as an immune system against TEs, and called PIWI-interacting RNAs (piRNAs) 1,2. In Drosophila, the production of piRNAs is initiated from heterochromatic loci containing remnants of TEs and enriched in histone H3 trimethylated on lysine 9 (H3K9me3) 3-5. These loci, called piRNA clusters, constitute a memory of past TE invasions. Little is known about how piRNA clusters are genetically defined. Using a genetic screen combined with a bimodal epigenetic state piRNA cluster (BX2), we identified the splicing factor Half pint (Hfp) and the histone demethylase KDM3 as being able to prevent BX2 piRNA production. Furthermore, we showed that Hfp is needed to splice Kdm3 transcripts. Germline expression of Kdm3 coding sequence (splicing-independent) rescued the hfp germline knock-down (GLKD) effect demonstrating that Kdm3 is sufficient to prevent BX2 piRNA production. Our data revealed that in the absence of Kdm3, dozens of gene-containing regions become bona fide germinal dual strand piRNA clusters. Indeed, they produce piRNAs originating from both DNA strands, become transcribed in a Moonshiner-dependent manner and enriched in di-and tri-methylation of lysine 9 of histone H3 (H3K9me2/3) and in Rhino, an HP1-like protein. Eggs laid by Kdm3 GLKD females do not hatch and show developmental defects phenocopying loss of function of genes included into the new piRNA clusters, suggesting an inheritance of functional ovarian "auto-immune" piRNAs. Our results demonstrate that some gene-containing regions are actively prevented for piRNA production by proteins that counteract piRNA cluster emergence. Hence, a non-piRNA-producing state is therefore not a "by default" state but rather a cellular lock that is actively controlled for some genomic loci. KEY FACTSO_LIHfp regulates the expression of Kdm3 via its splicing C_LIO_LIKdm3 prevents genomic regions containing coding genes from becoming piRNA clusters C_LIO_LIEmbryos from Kdm3 mutant females show developmental phenotypes suggesting that auto-immune piRNAs are functional and alter the expression of genes embedded in newly established piRNA clusters C_LI

genetics↗

bioRxiv2018

Environmentally-induced epigenetic conversion of a piRNA cluster

Transposable element (TE) activity is repressed in animal gonads by PIWI-interacting RNAs (piRNAs), a class of small RNAs produced by specific loci made of TEs insertions and fragments. Current models propose that these loci are functionally defined by the maternal inheritance of piRNAs produced during the previous generation, raising the question of their first activation in the absence of piRNAs. Taking advantage of an inactive cluster of P-element derived transgene insertions, we show here that raising flies at high temperature (29{degrees}C) instead of 25{degrees}C results in a rare but invasive epigenetic conversion of this locus into an active piRNAs producing one. The newly acquired epigenetic state is stable over many generations even when flies are switch back to 25{degrees}C. The silencing capacities, piRNA production and chromatin modifications of the cluster are all identical whether conversion occurred by maternal piRNA inheritance or by high temperature. We also demonstrate that in addition to high temperature, a single homologous transgene inserted elsewhere in the genome is required to activate the locus. We thus have identified a minimal system of three components to create a stable piRNA producing locus: 1) a locus with multiple TE derived sequences; 2) an euchromatic copy of these sequences and 3) elevated temperature. Altogether, these data report the first case of the establishment of an active piRNA cluster by environmental changes. It highlights how such variations of species natural habitat can become heritable and shape their epigenome.\n\nSIGNIFICANCE STATEMENTRecently, we have witnessed great progress in our understanding of the silencing of Transposable Elements (TEs) by piRNAs, a class of small RNAs produced by piRNA clusters. At each generation, piRNA clusters are supposed to be activated by homologous piRNAs inherited from the mother raising the question of the making of the first piRNAs. Here, we report the birth of a stable and functional piRNA cluster induced by high temperature without maternal inheritance of homologous piRNAs. We propose a minimal system to create a piRNA cluster: a sufficient number of repeated sequences, a euchromatic copy of these sequences and an increase in the production of antisense RNA.

genetics↗