About the project

The goal of the MetEpiClock Project, funded through an MCSA Global Fellowship and lead by Carolina Greco, is to investigate if metabolic pathways able to influence gene expression via chromatin dynamics are under circadian control and whether these regulatory networks are crucial for the maintenance of a correct metabolic homeostasis.

Recent interest and emphasize has been given to the study of the interconnection between cellular metabolism and epigenetic modifications and to the relationship of the latter with pathological conditions. The activity of most epigenetic enzymes is dependent on cellular levels of intermediate metabolites, coupling epigenetic driven transcriptional regulation with the metabolic state of the cell.

A the same time, almost all aspects of diurnal physiology are under circadian control, including numerous metabolic pathways. Defects in circadian rhythms influence physiology and behavior with implications for numerous pathological conditions, including cancer, metabolic syndrome, obesity, diabetes, cardiovascular diseases and neurodegenerative disorders. Whether a direct link between circadian regulation of metabolism and epigenetic dynamics exists is an open question, one that MetEpiClock will contribute to answer.

Associated publications

Carolina M. Greco#,*, Kevin B. Koronowski,*, Jacob G. Smith*, Jiejun Shi, Siwei Chen, Muntaha Samad, Patrick-Simon Welz, Valentina M. Zinna, Thomas Mortimer, Kohei Shimaji, Tomoki Sato, Paul Petrus, Shoko Sato, Cassandra Van, Jose Manual Monroy Kuhn, Kenneth A. Dyar, Dominik Lutter, Marcus M. Seldin, Wei Li, Pierre Baldi, Salvador Aznar Benitah#, Paolo Sassone-Corsi Integration of Feeding Behavior by the Liver Circadian Clock Reveals Network Dependency of Metabolic Rhythms Science Advances 2021 24;7(39)  # corresponding author; *These authors contributed equally

Kevin B. Koronowski*#, Carolina M. Greco*#, He Huang, Jin-Kwang Kim, Rachel Fellows, Jennifer Fribourgh, Lavina Mathur, Xuelian Ren, Carrie L. Partch, Cholsoon Jang, Feng Qiao, Yingming Zhao, Paolo Sassone-Corsi Ketogenesis Impact on Liver Metabolism Revealed by Proteomics of Lysine β-hydroxybutyrylation. Cell Reports 2021 3;36(5):109487 # corresponding author; * These authors contributed equally

Greco CM*, Cervantes M, Fustin JM, Ceglia N, Samad M, Shi J, Forne I, Imhof A, Li w, Baldi P, Okamura H, Sassone-Corsi P* S-Adenosyl-L-Homocysteine Hydrolase Links Methionine Metabolism to the Circadian Clock and Chromatin Remodeling Science Advances 2020 6(51):eabc5629 * Corresponding Author

Greco CM, Sassone-Corsi P. Personalized medicine and circadian rhythms: Opportunities for modern society J Exp Med. 2020 217(6):e20200702

Greco CM, Sassone-Corsi P. Circadian Blueprint of Metabolic Pathways in the Brain. Nat. Rev. Neuroscience 2019 20(2):71-82