Biology
Permanent link for this communityhttps://hdl.handle.net/2022/7910
Browse
Browsing Biology by Subject "Animals"
Now showing 1 - 5 of 5
- Results Per Page
- Sort Options
Item Analysis of model replication origins in Drosophila reveals new aspects of the chromatin landscape and its relationship to origin activity and the prereplicative complex(The American Society for Cell Biology, 2012) Liu, J.; Mconnell, K.; Dixon, M.; Calvi, B.R.Epigenetic regulation exerts a major influence on origins of DNA replication during development. The mechanisms for this regulation, however, are poorly defined. We showed previously that acetylation of nucleosomes regulates the origins that mediate developmental gene amplification during Drosophila oogenesis. Here we show that developmental activation of these origins is associated with acetylation of multiple histone lysines. Although these modifications are not unique to origin loci, we find that the level of acetylation is higher at the active origins and quantitatively correlated with the number of times these origins initiate replication. All of these acetylation marks were developmentally dynamic, rapidly increasing with origin activation and rapidly declining when the origins shut off and neighboring promoters turn on. Fine-scale analysis of the origins revealed that both hyperacetylation of nucleosomes and binding of the origin recognition complex (ORC) occur in a broad domain and that acetylation is highest on nucleosomes adjacent to one side of the major site of replication initiation. It was surprising to find that acetylation of some lysines depends on binding of ORC to the origin, suggesting that multiple histone acetyltransferases may be recruited during origin licensing. Our results reveal new insights into the origin epigenetic landscape and lead us to propose a chromatin switch model to explain the coordination of origin and promoter activity during development.Item Cryptocephal, the Drosophila melanogaster ATF4, Is a Specific Coactivator for Ecdysone Receptor Isoform B2(PLoS Genetics, 2012) Gauthier, S.A.; VanHaaften, E.; Cherbas, L.; Cherbas, P.; Hewes, R.S.The ecdysone receptor is a heterodimer of two nuclear receptors, the Ecdysone receptor (EcR) and Ultraspiracle (USP). In $\textit{Drosophila melanogaster}$, three EcR isoforms share common DNA and ligand-binding domains, but these proteins differ in their most N-terminal regions and, consequently, in the activation domains (AF1s) contained therein. The transcriptional coactivators for these domains, which impart unique transcriptional regulatory properties to the EcR isoforms, are unknown. Activating transcription factor 4 (ATF4) is a basic-leucine zipper transcription factor that plays a central role in the stress response of mammals. Here we show that Cryptocephal (CRC), the $\textit{Drosophila}$ homolog of ATF4, is an ecdysone receptor coactivator that is specific for isoform B2. CRC interacts with EcR-B2 to promote ecdysone-dependent expression of ecdysis-triggering hormone (ETH), an essential regulator of insect molting behavior. We propose that this interaction explains some of the differences in transcriptional properties that are displayed by the EcR isoforms, and similar interactions may underlie the differential activities of other nuclear receptors with distinct AF1-coactivators.Item Global Patterns of Tissue-Specific Alternative Polyadenylation in Drosophila(Cell Reports, 2012) Smibert, P.; Miura, P.; Westholm, J.O.; Shenker, S.; May, G.; Duff, M.O.; Zhang, D.; Eads, B.D.; Carlson, J.; Brown, J.B.; Eisman, R.C.; Andrews, J.; Kaufman, T.; Cherbas, P.; Celniker, S.E.; Graveley, B.R.; Lai, E.C.We analyzed the usage and consequences of alternative cleavage and polyadenylation (APA) in $\textit{Drosophila melanogaster}$ by using >1 billion reads of stranded mRNA-seq across a variety of dissected tissues. Beyond demonstrating that a majority of fly transcripts are subject to APA, we observed broad trends for 3′ untranslated region (UTR) shortening in the testis and lengthening in the central nervous system (CNS); the latter included hundreds of unannotated extensions ranging up to 18 kb. Extensive northern analyses validated the accumulation of full-length neural extended transcripts, and in situ hybridization indicated their spatial restriction to the CNS. Genes encoding RNA binding proteins (RBPs) and transcription factors were preferentially subject to 3′ UTR extensions. Motif analysis indicated enrichment of miRNA and RBP sites in the neural extensions, and their termini were enriched in canonical cis elements that promote cleavage and polyadenylation. Altogether, we reveal broad tissue-specific patterns of APA in $\textit{Drosophila}$ and transcripts with unprecedented 3′ UTR length in the nervous system.Item Natal-host environmental effects on juvenile size, transmission success, and operational sex ratio in the entomopathogenic nematode Steinernema carpocapsae(American Society of Parasitologists, 2012) Therese, M.O.; Bashey, F.Trans-host effects can alter the ecological and evolutionary dynamics of parasite and host populations. Here, we examine whether resource limitation within a parasite's natal host affects propagule size and influences parasite fitness in a new host. To alter resource competition, we infected caterpillars with 3 doses of the nematode Steinernema carpocapsae and harvested transmission-stage juveniles either early or late in the infection. We measured the size of these juveniles, and then we examined their ability to colonize and their sex ratio upon maturity in a new host. We found a trade-off between the cumulative number and size of nematodes emerging from a host. Emerging nematode size declined significantly over the time course of the infection, but dose had no significant effects. Larger, early emerging nematodes had greater success in colonizing a new host than smaller, later emerging nematodes, independently of whether they needed to locate the host. Furthermore, although early emerging nematodes resulted in an equal sex ratio in the new host, late emerging nematodes resulted in female-biased populations. These transmission and sex-ratio effects demonstrate that conditions in the natal host can affect parasite fitness, and they suggest that trans-host effects need to be more fully integrated into our studies of parasite populations.Item Tissue Damage Disrupts Developmental Progression and Ecdysteroid Biosynthesis in Drosophila(PLOS ONE, 2012) Hackney, J.F.; Zolali-Meybodi, O.; Cherbas, P.In humans, chronic inflammation, severe injury, infection and disease can result in changes in steroid hormone titers and delayed onset of puberty; however the pathway by which this occurs remains largely unknown. Similarly, in insects injury to specific tissues can result in a global developmental delay (e.g. prolonged larval/pupal stages) often associated with decreased levels of ecdysone – a steroid hormone that regulates developmental transitions in insects. We use $\textit{Drosophila melanogaster}$ as a model to examine the pathway by which tissue injury disrupts developmental progression. Imaginal disc damage inflicted early in larval development triggers developmental delays while the effects are minimized in older larvae. We find that the switch in injury response (e.g. delay/no delay) is coincident with the mid-3rd instar transition – a developmental time-point that is characterized by widespread changes in gene expression and marks the initial steps of metamorphosis. Finally, we show that developmental delays induced by tissue damage are associated with decreased expression of genes involved in ecdysteroid synthesis and signaling.