Periodic Reporting for period 2 - MetEpiClock (Circadian Control of Histone Methylation Dynamics through the Fine-tuning of Methionine Metabolic Flux)
Reporting period: 2019-11-01 to 2020-10-31
Chromatin plasticity relies on a variety of enzymes that are dependent on intermediary metabolites, thereby coupling metabolic pathways to epigenetic modifications and gene regulation. A feature of the metabolic-chromatin axis is the translocation of some metabolic enzymes into the nucleus and their contribution to localized availability of metabolites involved in epigenetic regulation. The methionine metabolic pathway intermediates S-adenosyl methionine (SAM) and S-adenosyl homocysteine (SAH), influence gene expression through epigenetic mechanisms as they activate and inhibit, respectively, the activity of enzymes that drive DNA and histone methylation.
The project aims at investigating a possible direct link between cellular metabolism, epigenetic dynamics and circadian rhythms. Results from MetEpiClock will uncover a functional crosstalk between the molecular clock and methionine metabolism.
Objectives:
1. To determine if key enzymes and metabolites of the methionine cycle display circadian expression and are clock controlled.
2. To elucidate if disruption of cellular methionine homeostasis affects circadian rhythms.
2.1 To investigate the effect of methionine metabolic perturbation on circadian gene expression in vitro.
2.2 To investigate the effect of methionine metabolic perturbation of circadian rhythms and metabolic homeostasis in vivo.