Balancing Act: Understanding metabolic regulation via the acetyltransferase MOF during Drosophila embryogenesis

forthcoming

The risk of prenatal onset of metabolic disorders is influenced by the maternal environment, which is inherited by the offspring through epigenetic modifications. Epigenetic modifications utilize metabolic substrates, highlighting the connection between epigenetics and metabolism. In Drosophila, one key epigenetic modification is the MOF-mediated acetylation of histone H4 at lysine 16 (H4K16ac), which is known to be intergenerationally transmitted from mother to embryo. This makes Drosophila an ideal model to study how maternally contributed epigenetic modifications and metabolites shape embryonic development. MOF operates in two modes: maternal pools establish chromatin accessibility, while zygotic pools facilitate future gene activation. Given that embryonic metabolism is temporally coordinated during development, the role of epigenetic regulation in embryonic metabolism remains unexplored. To address this, I plan to investigate the temporal contributions of MOF in metabolic regulation during Drosophila embryogenesis. Specifically, the following aims will be undertaken: Aim 1: Understand the maternal contributions of MOF-mediated metabolic regulation. Aim 2: Investigate the zygotic contributions of MOF in metabolic regulation. Aim 3: Uncover the association of MOF with the MSL or NSL complex to provide a mechanistic basis for metabolic regulation. These aims will be achieved through a combination of cutting-edge techniques involving metabolomics, RNA-sequencing, and epigenomics. This research will provide insights into metabolic regulation during early development and its implications for maternal impacts on offspring metabolism. The findings will enhance our understanding of the fundamental mechanisms underlying the epigenetic basis of metabolic regulation, with broader implications for developmental biology and disease.