Date of Award

2020

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Microbiology, Molecular Biology and Biochemistry

Abstract

MLR COMPASS-like complexes are highly-conserved epigenetic regulators required for enhancer establishment and subsequent reprogramming during differentiation and development. Mutation of MLR complex subunits in humans is associated with cancer and developmental disorder, yet much remains to be determined concerning both the healthy and disease-altered functions of these complexes. Using the developmental model Drosophila melanogaster, I further elucidate the functions of the MLR complex during in vivo organ development as well as stress response. I characterize the miRNa bantam as a regulatory target of the complex, required for proper tissue patterning during wing and compound eye formation. in the same systems I confirm in vitro evidence that the MLR complex is required to establish enhancers for regulatory activity cell generations before reprogramming, and further demonstrate a protective role against apoptosis in undifferentiated tissue. Using the fat body as a model of metabolic activity and stress response, I demonstrate that the depletion rate of triglyceride stores during nutrient stress is sensitive to MLR complex activity, and suggest that this is an indirect effect of the regulation of stress response signaling pathways. Through these investigations I demonstrate that the MLR complex may function to either promote or suppress the activity of a single transcriptional effector or the transcription of a single regulatory target, depending on the contexts of development and cell fate.

Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License.

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