The MLR COMPASS-like complex is required to regulate triglyceride depletion and stress response in the Drosophila fat body

MLR COMPASS-like complexes are highly conserved histone modifiers and enhancer regulators recruited by multiple transcription factors during differentiation and development, including lineage-determining factors, nuclear receptors, and developmental signaling pathway effectors. While the essential functions of MLR complexes during differentiation-associated transcriptional reprogramming has been well-explored, roles that these complexes play during reprogramming events in terminally differentiated cells remain understudied. We determined that the Drosophila MLR complex is required in fat body adipocytes for proper regulation of the triglyceride depletion rate during non-feeding periods, including metamorphosis and adult starvation. Transcriptome analysis revealed that the complex plays a critical role in controlling stress-related reprogramming in these cells, suggesting that the metabolic phenotypes are indirect effects of dysregulated stress transcription. Furthermore, our evidence suggests that the complex interacts with Foxo and Relish (Nf-κb) pathways and is required for proper expression of their targets. This investigation further elucidates the necessary functions of MLR complexes in regulating transcriptional reprogramming in terminally differentiated cells as well as suggests novel binding partners. Apparent roles for these complexes in the proper regulation of stress-induced transcription implies new mechanisms involved in cancer and other human diseases associated with MLR subunit mutation. ### Competing Interest Statement The authors have declared no competing interest.