DNA copy number evolution in Drosophila cell lines

Lee, Hangnoh; McManus, C. Joel; Cho, Dong-Yeon; Eaton, Matthew L.; Renda, Fioranna; Somma, Maria Patrizia; Cherbas, Lucy; May, Gemma E.; Powell, Sara; Zhang, Dayu; Zhan, Lijun; Resch, Alissa M.; Andrews, Justen; Celniker, S; Cherbas, Peter; Przytycka, Teresa M.; Gatti, Maurizio; Oliver, Brian; Graveley, Brenton R.; MacAlpine, David M.

doi:10.1186/gb-2014-15-8-r70

Cited by 100 publications

(181 citation statements)

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“…For example, bantam is generally highly expressed, and this miRNA is well known as a potent growth-promoting and apoptosis-inhibiting miRNA (Brennecke et al 2003). Interestingly, a companion study shows the bantam locus is a frequent target of copy number amplification across many modENCODE cell lines, providing a potential molecular rationale for its high expression across diverse cell lines (Lee et al 2014 …”

Section: Discussionmentioning

confidence: 99%

“…In principle, our current deep sequencing data sets might allow us to identify highly cell-specific miRNAs that might not be seen in sequencing data from whole animals or even tissues, which are often composed of a diversity of cell types. In addition, given that these cell lines harbor chromosomal aberrations and aneuploidy (Lee et al 2014), an intriguing possibility is that their mutated genomes may generate novel transcribed regions that are sources of miRNAs.…”

Section: Org Downloaded Frommentioning

confidence: 99%

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Diversity of miRNAs, siRNAs, and piRNAs across 25 Drosophila cell lines

et al. 2014

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We expanded the knowledge base for Drosophila cell line transcriptomes by deeply sequencing their small RNAs. In total, we analyzed more than 1 billion raw reads from 53 libraries across 25 cell lines. We verify reproducibility of biological replicate data sets, determine common and distinct aspects of miRNA expression across cell lines, and infer the global impact of miRNAs on cell line transcriptomes. We next characterize their commonalities and differences in endo-siRNA populations. Interestingly, most cell lines exhibit enhanced TE-siRNA production relative to tissues, suggesting this as a common aspect of cell immortalization. We also broadly extend annotations of cis-NAT-siRNA loci, identifying ones with common expression across diverse cells and tissues, as well as cell-restricted loci. Finally, we characterize small RNAs in a set of ovary-derived cell lines, including somatic cells (OSS and OSC) and a mixed germline/somatic cell population (fGS/ OSS) that exhibits ping-pong piRNA signatures. Collectively, the ovary data reveal new genic piRNA loci, including unusual configurations of piRNA-generating regions. Together with the companion analysis of mRNAs described in a previous study, these small RNA data provide comprehensive information on the transcriptional landscape of diverse Drosophila cell lines. These data should encourage broader usage of fly cell lines, beyond the few that are presently in common usage.

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Section: Discussionmentioning

confidence: 99%

Section: Org Downloaded Frommentioning

confidence: 99%

Diversity of miRNAs, siRNAs, and piRNAs across 25 Drosophila cell lines

et al. 2014

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“…DNA bound to dFOXO was cross-linked and the chromatin associated was immunoprecipitated with antibodies to dFOXO (6,18). Precipitated DNA was analyzed on Affymetrix tiling arrays and compared with input DNA to control for possible copy number variation in the cells (19). Using a cutoff of fourfold enrichment over input, we identified ∼2,200 genes that were bound by dFOXO (Dataset S1).…”

Section: Resultsmentioning

confidence: 99%

FOXO regulates RNA interference in Drosophila and protects from RNA virus infection

Spellberg

Marr

2015

Proc. Natl. Acad. Sci. U.S.A.

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Small RNA pathways are important players in posttranscriptional regulation of gene expression. These pathways play important roles in all aspects of cellular physiology from development to fertility to innate immunity. However, almost nothing is known about the regulation of the central genes in these pathways. The forkhead box O (FOXO) family of transcription factors is a conserved family of DNAbinding proteins that responds to a diverse set of cellular signals. FOXOs are crucial regulators of cellular homeostasis that have a conserved role in modulating organismal aging and fitness. Here, we show that Drosophila FOXO (dFOXO) regulates the expression of core small RNA pathway genes. In addition, we find increased dFOXO activity results in an increase in RNA interference (RNAi) efficacy, establishing a direct link between cellular physiology and RNAi. Consistent with these findings, dFOXO activity is stimulated by viral infection and is required for effective innate immune response to RNA virus infection. Our study reveals an unanticipated connection among dFOXO, stress responses, and the efficacy of small RNA-mediated gene silencing and suggests that organisms can tune their gene silencing in response to environmental and metabolic conditions.O rganisms must be able to respond to changing conditions to survive. Radical changes in environment or metabolism can induce cellular stress signaling pathways meant to help the cell return to a normal range of function. Whereas there are dedicated transcriptional response pathways to deal with specific individual stresses such as heat shock (HSF) (1) or heavy metals (MTF-1) (2), the forkhead box O (FOXO) pathway has emerged as a general stress responsive transcription factor. Although initially characterized as downstream targets of insulin signaling, it is now clear that the FOXOs respond to multiple cellular stress signaling pathways including nutrient deprivation, oxidative stress, mitochondrial dysfunction, DNA damage, bacterial infection, and other cellular stress signals (3, 4).The FOXO family of transcription factors is conserved from Caenorhabditis elegans to humans. Invertebrates have a single FOXO gene: daf-16 in worms and dFOXO in Drosophila (5, 6). In mammals, the four FOXO genes (FOXO1, FOXO3, FOXO4, and FOXO6) have diversified, with some factors having a stressspecific response (7-10). Therefore, invertebrates offer a particularly attractive system for understanding FOXO function because the single isoform is responsible for all of the roles of the four mammalian FOXOs.Small noncoding RNA pathways are capable of regulating gene expression in a sequence-specific manner (11). Effector complexes called RNA-induced silencing complexes (RISC) containing small single-stranded RNAs bound to Argonaute proteins find target mRNAs and posttranscriptionally prevent their expression. Three major small RNA pathways have been identified in animal cells, the microRNA (miRNA) pathway, the small interfering RNA pathway (siRNA), and PIWI RNA (piRNA) pathways, each contain uni...

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“…Depletion of either DCC component, MOF or MSL2, resulted in a loss of X chromosome-specific H4K16 hyperacetylation as expected. It should be noted that the H4K16 hyperacetylation occurs on multiple different mitotic figures, and this is due to the inherent aneuploidy of the S2 genome, which features a large number of chromosomal copy number variations as well as structural rearrangements and translocations Lee et al 2014). Control cells and those treated with a nonspecific scrambled siRNA (pUC19) exhibited preferential early EdU incorporation on the X chromosome (40.6% and 37.3% of metaphase spreads, respectively), while no such enrichment was detected in DCC knockdown cells (Fig.…”

Section: Promotes Early Replication Of the X Chromosomementioning

confidence: 99%

DNA replication and transcription programs respond to the same chromatin cues

et al. 2014

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DNA replication is a dynamic process that occurs in a temporal order along each of the chromosomes. A consequence of the temporally coordinated activation of replication origins is the establishment of broad domains (>100 kb) that replicate either early or late in S phase. This partitioning of the genome into early and late replication domains is important for maintaining genome stability, gene dosage, and epigenetic inheritance; however, the molecular mechanisms that define and establish these domains are poorly understood. The modENCODE Project provided an opportunity to investigate the chromatin features that define the Drosophila replication timing program in multiple cell lines. The majority of early and late replicating domains in the Drosophila genome were static across all cell lines; however, a small subset of domains was dynamic and exhibited differences in replication timing between the cell lines. Both origin selection and activation contribute to defining the DNA replication program. Our results suggest that static early and late replicating domains were defined at the level of origin selection (ORC binding) and likely mediated by chromatin accessibility. In contrast, dynamic domains exhibited low ORC densities in both cell types, suggesting that origin activation and not origin selection governs the plasticity of the DNA replication program. Finally, we show that the male-specific early replication of the X chromosome is dependent on the dosage compensation complex (DCC), suggesting that the transcription and replication programs respond to the same chromatin cues. Specifically, MOF-mediated hyperacetylation of H4K16 on the X chromosome promotes both the up-regulation of male-specific transcription and origin activation.

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DNA copy number evolution in Drosophila cell lines

Cited by 100 publications

References 96 publications

Diversity of miRNAs, siRNAs, and piRNAs across 25 Drosophila cell lines

Diversity of miRNAs, siRNAs, and piRNAs across 25 Drosophila cell lines

FOXO regulates RNA interference in Drosophila and protects from RNA virus infection

DNA replication and transcription programs respond to the same chromatin cues

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