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Hwangbo, D.-S.

Publications and source records attributed to Hwangbo, D.-S..

3 recordsLinked to original sources

Temperature-driven coordination of circadian transcriptome regulation

The circadian rhythm is an evolutionarily-conserved molecular oscillator that enables species to anticipate rhythmic changes in their environment. At a molecular level, the core clock genes induce a circadian oscillation in thousands of genes in a tissue-specific manner, orchestrating myriad biological processes. While studies have investigated how the core clock circuit responds to environmental perturbations such as temperature, the downstream effects of such perturbations on circadian regulation remain poorly understood. By analyzing bulk-RNA sequencing of Drosophila fat bodies harvested from flies subjected to different environmental conditions, we demonstrate a highly condition-specific circadian transcriptome. Further employing a reference-based gene regulatory network (Reactome), we find evidence of increased gene-gene coordination at low tem-peratures and synchronization of rhythmic genes that are network neighbors. Our results point to the mechanisms by which the circadian clock mediates the flys response to seasonal changes in temperature. Significance StatementThe circadian rhythm enables organisms to anticipate and adapt to changes in their environment. While behavioral changes have been observed in Drosophila melanogaster subjected to low temperatures, little is known regarding how these changes are enacted at a molecular level. By conducting bulk RNA sequencing from fruit flies, we observe that genome-wide circadian oscillation patterns are temperature dependent. Intriguingly, we find that morning and evening peaks of transcriptomic activity shift closer together, consistent with anticipation of a shorter photoperiod in cooler winter weather. We further find that the low-temperature dynamics are highly coordinated with respect to a reference-based gene regulatory network. Our findings provide insights into the mechanisms by which flies adapt to environmental temperature changes.

bioinformatics↗

Dietary Restriction Fails to Extend Lifespan of Drosophila Model of Werner Syndrome

Werner syndrome (WS) is a rare genetic disease in humans, caused by mutations in the WRN gene that encodes a protein containing helicase and exonuclease domains. WS is characterized by symptoms of accelerated aging in multiple tissues and organs, involving increased risk of cancer, heart failure, and metabolic dysfunction. These conditions ultimately lead to the premature mortality of patients with WS. In this study, using the null mutant flies (WRNexo{Delta}) for the gene WRNexo (CG7670), homologous to the exonuclease domain of WRN in humans, we examined how diets affect the lifespan, stress resistance, and sleep/wake patterns of a Drosophila model of WS. We observed that dietary restriction (DR), one of the most robust non-genetic interventions to extend lifespan in animal models, failed to extend the lifespan of WRNexo{Delta} mutant flies and even had a detrimental effect in females. Interestingly, the mean lifespan of WRNexo{Delta} mutant flies was not reduced on a protein-rich diet compared to that of wild-type flies. Compared to wild type control flies, the mutant flies also exhibited altered responses to DR in their resistance to starvation and oxidative stress, as well as changes in sleep/wake patterns. These findings show that the WRN protein is necessary for mediating the effects of DR and suggest that the exonuclease domain of WRN plays an important role in metabolism in addition to its primary role in DNA repair and genome stability. Our results also raise the possibility that diet-mediated interventions could ameliorate the symptoms of WS.

genetics↗

Dietary Restriction Impacts Peripheral Circadian Clock Output Important for Longevity in Drosophila

Circadian clocks may mediate lifespan extension by caloric or dietary restriction (DR). We find that the core clock transcription factor Clock is crucial for a robust longevity and fecundity response to DR in Drosophila. To identify clock-controlled mediators, we performed RNA-sequencing from abdominal fat bodies across the 24 h day after just 5 days under control or DR diets. In contrast to more chronic DR regimens, we did not detect significant changes in the rhythmic expression of core clock genes. Yet we discovered that DR induced de novo rhythmicity or increased expression of rhythmic clock output genes. Network analysis revealed that DR increased network connectivity in one module comprised of genes encoding proteasome subunits. Adult, fat body specific RNAi knockdown demonstrated that proteasome subunits contribute to DR-mediated lifespan extension. Thus, clock control of output links DR-mediated changes in rhythmic transcription to lifespan extension.

genetics↗