Myc plays an important role in Drosophila P-M hybrid dysgenesis to eliminate germline cells with genetic damage

Ota, Ryoma; Kobayashi, Satoru

doi:10.1038/s42003-020-0923-3

Cited by 8 publications

(15 citation statements)

References 58 publications

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“…Indeed, all of the major chorion genes were found to be significantly upregulated in the tolerant genotypes (Figure 2c, Tootle et al 2011;Kim et al 2011). It is unlikely that chorion assembly impacts dysgenic ovarian atrophy, since chorion synthesis occurs in late-stage oocytes (stages 10B-14, G. L. , whereas atrophy results from the loss of larval primordial germline cells and subsequent germline stem cells (GSCs) (Dorogova et al, 2017;Ota & Kobayashi, 2020;Tasnim & Kelleher, 2018;Teixeira et al, 2017). However, chorion genes reside in clusters that undergo amplification (Claycomb et al, 2004;Spradling, 1981), a process that relies on the efficient repair of DSBs at the boundaries of an amplified region (Alexander et al, 2015).…”

Section: Resultsmentioning

confidence: 99%

“…In larval neuroblasts, TIP60 and Myc coregulate downstream targets that promote stem cell self-renewal (Rust et al, 2018). Similarly, myc overexpression confers tolerance in dysgenic larval gonads by suppressing primordial germ cell (PGC) loss (Ota & Kobayashi, 2020). Thus, increased TIP60 function in tolerant genotypes may activate myc-dependent tolerance in larvae.…”

Section: Discussionmentioning

confidence: 99%

“…Alternatively, tolerance could arise by weakening the connection between DNA damage and germline loss, allowing dysgenic individuals to maintain gametogenesis but produce gametes with more mutations. For example, overexpression of the stem cell self-renewal factor myc is associated with suppressed germline loss in dysgenic males and females, resulting in the production of additional gametes that exhibit more P-element transpositions (Ota & Kobayashi, 2020).…”

Section: Introductionmentioning

confidence: 99%

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Natural tolerance to transposition is associated with double-strand break repair and germ-cell differentiation

Lama

Srivastav²,

Tasnim³

et al. 2021

Preprint

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Transposable elements (TE) are mobile genetic parasites whose unregulated activity in the germline causes DNA damage and sterility. In multiple species of Drosophila, P-element transposition in larval primordial germ cells (PGCs), as well as adult germline stem cells (GSCs), leads to the loss of both cell types and in extreme cases: agametic gonads. While much is known about the regulation of P-element transposition by piRNAs, less is known about tolerance factors that could allow PGCs or GSCs to persist in the face of high transposition rates. Using a panel of highly recombinant inbred lines of Drosophila melanogaster, we identified two linked quantitative trait loci (QTL) associated with natural variation in tolerance to P-element transposition. By comparing the total RNA and small RNA pools of multiple tolerant and sensitive genotypes, we found that sensitive genotypes upregulate histones and translational machinery, while tolerant genotypes upregulate chorion proteins. We further observed that sensitive genotypes exhibit increased expression of pericentromeric genes, suggesting reduced heterochromatin formation. Based on these differentially expressed genes and functional classes, location within a QTL, and in-phase single nucleotide polymorphisms (SNPs), we identified two candidate genes that we propose influence tolerance: brat and Nipped-A. Both candidates are known interactors of the tolerance factor myc, a conserved transcription factor whose activity promotes the retention of PGCs that are damaged by P-element transposition. brat is a translational repressor of myc, whereas Nipped-A is a co-factor that promotes the expression of genes involved in stem cell self renewal. Nipped-A also contributes to double-strand break (DSB) repair as a member of the Tat interactive protein 60-kDa (TIP60) complex, which could promote tolerance by repairing damage caused by transposition. Together our findings reveal complex underpinnings to natural variation in tolerance, including the modulated regulation of stem cell maintenance and DNA repair pathways.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Natural tolerance to transposition is associated with double-strand break repair and germ-cell differentiation

Lama

Srivastav²,

Tasnim³

et al. 2021

Preprint

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“…Immunofluorescence staining of embryos was performed as described 35 , 36 . The following experiments were conducted at room temperature unless otherwise stated.…”

Section: Methodsmentioning

confidence: 99%

Absence of X-chromosome dosage compensation in the primordial germ cells of Drosophila embryos

Ota

Hayashi

Morita

et al. 2021

Sci Rep

Self Cite

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Dosage compensation is a mechanism that equalizes sex chromosome gene expression between the sexes. In Drosophila, individuals with two X chromosomes (XX) become female, whereas males have one X chromosome (XY). In males, dosage compensation of the X chromosome in the soma is achieved by five proteins and two non-coding RNAs, which assemble into the male-specific lethal (MSL) complex to upregulate X-linked genes twofold. By contrast, it remains unclear whether dosage compensation occurs in the germline. To address this issue, we performed transcriptome analysis of male and female primordial germ cells (PGCs). We found that the expression levels of X-linked genes were approximately twofold higher in female PGCs than in male PGCs. Acetylation of lysine residue 16 on histone H4 (H4K16ac), which is catalyzed by the MSL complex, was undetectable in these cells. In male PGCs, hyperactivation of X-linked genes and H4K16ac were induced by overexpression of the essential components of the MSL complex, which were expressed at very low levels in PGCs. Together, these findings indicate that failure of MSL complex formation results in the absence of X-chromosome dosage compensation in male PGCs.

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“…The study of how Drosophila regulates P-element control is still an active and important topic. For example, P-elements have completely invaded nearly all wild Drosophila populations, but interplay between how quickly the piRNA pathway adapts to controlling P-element silencing is still being investigated [ 229 , 230 , 231 ]. An outstanding question is determining to what extent P-element copy number affects the severity of hybrid dysgenesis.…”

Section: Is the Role Of Active Transposons Causing Hybrid Fertilitmentioning

confidence: 99%

Diverse Defenses: A Perspective Comparing Dipteran Piwi-piRNA Pathways

Gamez

Srivastav

Akbari

et al. 2020

Cells

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Animals face the dual threat of virus infections hijacking cellular function and transposons proliferating in germline genomes. For insects, the deeply conserved RNA interference (RNAi) pathways and other chromatin regulators provide an important line of defense against both viruses and transposons. For example, this innate immune system displays adaptiveness to new invasions by generating cognate small RNAs for targeting gene silencing measures against the viral and genomic intruders. However, within the Dipteran clade of insects, Drosophilid fruit flies and Culicids mosquitoes have evolved several unique mechanistic aspects of their RNAi defenses to combat invading transposons and viruses, with the Piwi-piRNA arm of the RNAi pathways showing the greatest degree of novel evolution. Whereas central features of Piwi-piRNA pathways are conserved between Drosophilids and Culicids, multiple lineage-specific innovations have arisen that may reflect distinct genome composition differences and specific ecological and physiological features dividing these two branches of Dipterans. This perspective review focuses on the most recent findings illuminating the Piwi/piRNA pathway distinctions between fruit flies and mosquitoes, and raises open questions that need to be addressed in order to ameliorate human diseases caused by pathogenic viruses that mosquitoes transmit as vectors.

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Myc plays an important role in Drosophila P-M hybrid dysgenesis to eliminate germline cells with genetic damage

Cited by 8 publications

References 58 publications

Natural tolerance to transposition is associated with double-strand break repair and germ-cell differentiation

Natural tolerance to transposition is associated with double-strand break repair and germ-cell differentiation

Absence of X-chromosome dosage compensation in the primordial germ cells of Drosophila embryos

Diverse Defenses: A Perspective Comparing Dipteran Piwi-piRNA Pathways

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