Interaction with B-type lamin reveals the function of Drosophila Keap1 xenobiotic response factor in nuclear architecture.

BACKGROUND: The Keap1-Nrf2 pathway serves as a central regulator that mediates transcriptional responses to xenobiotic and oxidative stimuli. Recent studies have shown that Keap1 and Nrf2 can regulate transcripts beyond antioxidant and detoxifying genes, yet the underlying mechanisms remain unclear. Our research has uncovered that Drosophila Keap1 (dKeap1) and Nrf2 (CncC) proteins can control high-order chromatin structure, including heterochromatin. METHODS AND RESULTS: In this study, we identified the molecular interaction between dKeap1 and lamin Dm0, the Drosophila B-type lamin responsible for the architecture of nuclear lamina and chromatin. Ectopic expression of dKeap1 led to an ectopic localization of lamin to the intra-nuclear area, corelated with the spreading of the heterochromatin marker H3K9me2 into euchromatin regions. Additionally, mis-regulated dKeap1 disrupted the morphology of the nuclear lamina. Knocking down of dKeap1 partially rescued the lethality induced by lamin overexpression, suggesting their genetic interaction during development. CONCLUSIONS: The discovered dKeap1-lamin interaction suggests a novel role for the Keap1 oxidative/xenobiotic response factor in regulating chromatin architecture.

Drosophila Keap1 xenobiotic response factor regulates developmental transcription through binding to chromatin.

The Keap1-Nrf2 complex is a central regulator that mediates transcriptional responses to xenobiotic stimuli and is highly related with multiple human diseases. The molecular mechanisms and biological functions of Keap1 and Nrf2 are not fully understood. The Drosophila Keap1 homolog (dKeap1) is conserved with mammalian Keap1 except that dKeap1 contains a 156 aa C-terminal tail (CTD). A dKeap1 truncation with the CTD removed (dKeap1-ΔCTD) shows abolished nuclear localization and chromatin-binding. Expression of dKeap1-ΔCTD in the dKeap1 null background significantly rescues this mutant to the adult stage, but the files showed partial lethality, sterility and defects in adipose tissue. In the rescued flies, expression levels of ecdysone-response genes, ecdysone-synthetic genes and adipogenesis genes were down-regulated in specific tissues, indicating that the chromatin-binding of dKeap1 mediates the activation of these developmental genes. At the same time, dKeap1-ΔCTD can still suppress the basal expression of detoxifying genes and mediate the activation of these genes in response to xenobiotic stimuli, suggesting that the chromatin-binding of dKeap1 is not required for the regulation of detoxifying genes. These results support a model in which dKeap1 on one hand functions as an inhibitor for the Nrf2-mediated transcription in the xenobiotic response pathway and on the other hand functions as a chromatin-binding transcription activator in the developmental pathway. Our study reveals a novel mechanism whereby Keap1-Nrf2 xenobiotic response signaling regulates development using a mechanism independent of redox signaling.

Koi (Cyprinus rubrofuscus) Seek Out Tactile Interaction with Humans: General Patterns and Individual Differences.

The study of human-animal interactions has provided insights into the welfare of many species. To date, however, research has largely focused on human relationships with captive mammals, with relatively little exploration of interactions between humans and other vertebrates, despite non-mammals constituting the vast majority of animals currently living under human management. With this study, we aimed to address this gap in knowledge by investigating human-fish interactions at a community garden/aquaponics learning-center that is home to approximately 150 goldfish (Carassius auratus) and seven adult and two juvenile koi (Cyprinus rubrofuscus). After a habituation period (July-September 2019) during which time the fish were regularly provided with the opportunity to engage with the researcher's submerged hand, but were not forced to interact with the researcher, we collected video data on 10 non-consecutive study days during the month of October. This procedure produced 18~20-min interaction sessions, 10 during T1 (when the experimenter first arrived and the fish had not been fed) and eight during T2 (20-30 min after the fish had been fed to satiation; two sessions of which were lost due equipment malfunction). Interactions between the researcher and the seven adult koi were coded from video based on location (within reach, on the periphery, or out of reach from the researcher) and instances of physical, tactile interaction. Analyses revealed that overall, koi spent more time than expected within reach of the researcher during both T1 (p < 0.02) and T2 (p < 0.03). There were also substantial differences between individuals' overall propensity for being within-reach and engaging in physical interaction. These results show that koi will voluntarily interact with humans and that individual koi display unique and consistent patterns of interaction. By providing quantitative data to support anecdotal claims that such relationships exist around the world, this research contributes to the ongoing discoveries highlighting the profound dissonance between how humans think about and treat fish and who fish actually are, thereby emphasizing the necessity of stronger moral and legal protections for fishes.