Biology subjects

LABBE, C.

Publications and source records attributed to LABBE, C..

3 recordsLinked to original sources

bioRxiv2026

U1 snRNA blockade regulates DNA repair genes, DNA damage, and cisplatin sensitivity of lung cancer cells

Previous studies revealed a crosstalk between intronic polyadenylation (IPA) and the DNA damage response (DDR). Indeed, genotoxic agents, including radiations and anticancer drugs (e.g., cisplatin that crosslinks DNA), regulate the ratio of IPA to last-exon transcripts in many genes. Conversely, multiple genes involved in the DDR, especially homologous recombination, are regulated at the IPA level. The U1 small nuclear RNA (snRNA) widely represses IPA, thereby enhancing full-length gene transcription. However, besides its implication in IPA regulation by ultraviolet-C radiation, little is known about U1 snRNA effects on the DDR and on cell sensitivity to genotoxic agents. Here, we show that U1 snRNA blockade using an antisense oligonucleotide (U1-AMO) in lung cancer cell lines enhances cell growth inhibition by cisplatin, through an increase in cisplatin-induced DNA damage. 3-seq analysis indicates that U1 snRNA blockade represses full-length mRNA expression of multiple genes of the nucleotide-excision repair and Fanconi anemia pathways, which are involved in the repair of cisplatin-DNA crosslinks. Our 3-seq analyses also reveal that moderate doses of U1-AMO and cisplatin upregulate the IPA:LE isoform ratio in overlapping but distinct sets of genes, and that U1-AMO prevents cisplatin effects on the IPA:LE ratio in a large subset of genes. Altogether, these data extend the crosstalk between IPA and the DDR and suggest that U1 snRNA targeting may be used to sensitize cancer cells to genotoxic agents.

molecular biology↗

bioRxiv2022

EPIGENETIC LANDSCAPE OF HEAT STRESS INTERGENERATIONAL INHERITANCE IN A TELEOST FISH

Epigenetic information is transmitted from cell to cell, and even generation to generation. The question of epigenetic inheritance in fish has become of crucial interest in the recent years, when the mammalian model of methylome erasure in germ cells and embryos was found not to be conserved. Fish, which are particularly exposed to environmental variations might thus be prone to transmit epigenetic alterations to their offspring, driving rapid environmental acclimation. Here, by sequencing spermatozoa and muscle methylomes, we characterized the methylation landscape of paternal gametes in rainbow trout and demonstrated its sensitivity to a 4{degrees}C increased rearing temperature during spermatogenesis. We found that spermatozoa methylome primes housekeeping and developmental genes for activation and might be instrumental to early development. Most of these methylation-free promoters were not affected by temperature, attesting the robustness of the epigenetic programming of early development. However, the increase of temperature triggered the differential methylation of 5,359 regions, among which 560 gene promoters control spermiogenesis and lipid metabolism. We therefore report, for the first time in fish, that sperm epigenetic landscape carries marks of parental environmental conditions. In the context of a 4{degrees}C temperature increase during spermatogenesis, we describe how rainbow trout sperm DNA methylation might be a molecular basis of intergenerational inheritance and question its role in controlling next generations performances and acclimation to climate change.

genomics↗

bioRxiv2022

Reprogramming of fish somatic cells for nuclear transfer is primed by Xenopus egg extract

Somatic cell reprogramming in vitro prior to nuclear transfer is one strategy expected to improve clone survival during development. In this study, we investigated the reprogramming extent of fish fin somatic cells after in vitro exposure to Xenopus egg extract and subsequent culture. Using a cDNA microarray approach, we observed drastic changes in the gene expression profile of the treated cells. Several actors of the TGF{beta} and Wnt/{beta}-catenin signaling pathways, as well as some mesenchymal markers, were inhibited in treated cells, while several epithelial markers were upregulated. This was associated with morphological changes of the cells in culture, suggesting that egg extract drove somatic cells towards a mesenchymal-epithelial transition (MET), the hallmark of somatic reprogramming in induced pluripotent stem cells (iPSCs). However, treated cells were also characterized by a strong decrease in de novo lipid biosynthesis metabolism, the lack of re-expression of pou2 and nanog pluripotency markers, and absence of DNA methylation remodeling of their promoter region. In all, this study showed that Xenopus egg extract treatment initiated an in vitro reprogramming of fin somatic cells in culture. Although not thorough, the induced changes have primed the somatic chromatin for a better embryonic reprogramming upon nuclear transfer.

cell biology↗