Biology subjects

Iovino, N.

Publications and source records attributed to Iovino, N..

3 recordsLinked to original sources

bioRxiv2025

Cell cycle dynamics regulate H3K27 and H3K9 histone modifications

Cell cycle progression presents a fundamental challenge to genome integrity, particularly due to the need to reestablish post-translational histone modifications (PTMs) following DNA replication. Although proliferative and differentiating tissues exhibit markedly different cell cycle dynamics, how these differences shape the histone modification landscape in vivo remains largely unexplored. Here, we show that levels of H3K27ac, H3K27me3, and H3K9me3 are tightly linked to cell cycle dynamics in the Drosophila wing imaginal disc. We demonstrate that both physiological and pathological elongation of the cell cycle led to an accumulation of H3K9me3 and H3K27me3, whereas cell cycle acceleration reduces their levels. In contrast, H3K27ac exhibits the opposite pattern: levels decrease in arrested cells and increase with faster cycling. Genome-wide CUT&Tag analysis reveals that these changes predominantly affect genomic loci already modified in normally proliferating tissue. Importantly, the regulation of methylation levels at H3K9 and H3K27 is not solely mediated by the cell cycle machinery but reflects a metabolically guided process in which the rate of methylation is coupled to the rate of cell proliferation through metabolic activity, including signaling via the Insulin/PI3K/Akt pathway. Our study thus reveals key principles for understanding histone methylation in proliferating, senescent, and differentiating cells. In contrast, H3K27 acetylation is regulated through a distinct, cell cycle-coupled mechanism. We find that CBP/Nejire-mediated acetylation of H3K27 peaks during S-phase and is reversed by HDAC1, as cells exit replication. Disruption of this acetylation cycle leads to replication stress and a G2 cell cycle arrest via a DNA damage checkpoint. Notably, this genome-protective function of CBP/Nejire depends specifically on acetylation of the H3K27 residue itself, revealing a novel role for H3K27ac beyond its well-established function in transcriptional activation. Together, our findings establish a robust link between cell cycle progression and histone modification dynamics, highlighting the necessity of maintaining balanced PTM levels under varying proliferative states. These insights have broad implications for our understanding of development, aging, and tumor growth.

cell biology↗

bioRxiv2024

Embryonic piRNAs target horizontally transferred vertebrate transposons in assassin bugs

Piwi proteins and the associated Piwi-interacting RNAs (piRNAs) coordinate a surveillance system that protects the animal genome from DNA damage induced by transposable element (TE) mobilization. While the pathway has been described in detail in the fruit fly Drosophila melanogaster, much less is known in more basal insects. Here, we investigated the adaptation of the piRNA pathway to horizontally transferred transposons (HTTs) in the assassin bug Rhodnius prolixus, a primary vector of Chagas disease. Rhodnius acquired specific classes of HTTs by feeding on bats, opossums and squirrel monkeys. By analyzing the temporal dynamics of piRNA cluster expression and piRNA production during critical stages of Rhodnius development, we show that peak levels of [~]28 nt long piRNAs correlate with reduced HTT and resident TE expression primarily during embryogenesis. Strikingly, while resident TEs piRNAs seem to engage in a typical ping-pong amplification mechanism, sense and antisense HTT piRNAs instead overlap by [~]20 nt or do not display ping-pong signatures. These features are explained at least in part by the low number of HTT copies inserted into the piRNA clusters and might point to a non-canonical mechanism of biogenesis. Our data reveal that the piRNA, but not the siRNA pathway, responded to HTTs that were recently transferred from vertebrate tetrapods to a hematophagous insect of medical relevance.

genomics↗

bioRxiv2020

Transovarial transmission fuels persistent infections of a core virome in the Chagas disease vector Rhodnius prolixus

Triatomine assassin bugs comprise hematophagous insect vectors of Trypanosoma cruzi, the causative agent of the Chagas disease. Although the microbiome of these species has been investigated to some extent, only one virus infecting Triatoma infestans has been identified to date. Here, we describe for the first time seven (+) single-strand RNA viruses (RpV1-7) infecting Rhodnius prolixus, a primary vector of the Chagas disease in Central and South America. We show that the RpVs belong to the Picorna-Calici, Permutotetra and Luteo-Sobemo clades and are vertically transmitted from the mothers to the progeny via transovarial transmission. Consistent with this, all the RpVs, except RpV2 that is related to the entomopathogenic Slow bee paralysis virus, established persistent infections in our R. prolixus colony. Furthermore, we show that R. prolixus ovaries express 22-nucleotide viral siRNAs (vsiRNAs), but not viral piRNAs, that originate from the processing of dsRNA intermediates during viral replication of the RpVs. Interestingly, the Permutotetra and Luteo-Sobemo viruses display shared pools of visRNAs that might provide the basis for a cross-immunity system. The vsiRNAs are maternally deposited in the eggs, where they likely contribute to reduce the viral load and protect the developing embryos. Our results unveil for the first time a complex core virome in R. prolixus and begin to shed light on the RNAi-based antiviral defenses in triatomines. Author summaryRhodnius prolixus is a triatomine insect and a primary vector of Trypanosoma cruzi, the etiologic agent of the Chagas disease, in Central and South America. Despite the medical relevance, very little is known about the viruses that infect these so-called assassin bugs. In this study, we show for the first time that triatomines can support the concomitant infection of a variety of RNA viruses belonging to distantly related viral families. Remarkably, we show that the viruses are vertically transmitted from the mothers to the progeny via transovarial transmission. The detection of 22-nucleotide viral small interfering RNAs in mature eggs strongly suggests that RNAi mechanisms contribute to reduce the viral load during oogenesis and embryogenesis in R. prolixus, thus safeguarding the development of embryos and nymphs. In agreement with these findings, all the viruses, except one, could establish persistent infections in our colony. Our results substantially expand the knowledge of the virus complexity in triatomine species. This viral toolkit might be harnessed to develop novel insect population control strategies to reduce the diffusion of the Chagas disease.

immunology↗