Subsequent projects

Prof. Dr. Axel Imhof

Ludwig-Maximilians-University of Munich
Adolf-Butenandt-Institut, Department of Biochemistry

Prof. Dr. Paolo Sassone-Corsi

University of California, Irvine
Department of Pharmacology

Metabolic effects on post-translational protein modifications

Posttranslational protein modifications are crucially dependent on metabolic changes within a cell as the modifying enzymes use key metabolites as cofactors. As the Sassone-Corsi lab has shown metabolites change quite dramatically with a circadian rhythmicity. Together with the lab at UC Irvine, we have established an analysis pipeline for the investigation of lysine acetylations during the circadian cycle, and will now use this platform to investigate the effects of the levels of Acetyl-CoA on the global acetylome by manipulating key metabolic enzymes. Furthermore we will extend our studies to analyse the circadian changes of arginine and lysine methylation and their cofactor S-Adenosyl Methionine (SAM) by using heavy methyl SILAC labelling and the quantification of SAM. This will provide the essential groundwork for a better understanding of the effect of an altered metabolism on epigenetic inheritance, for which evidence so far has largely been provided by epidemiological studies. 

Primary project: Epigenetic effects of metabolic variation

Final Report

During the sequel of the BaCaTeC project we extended our analysis of posttranslational modifications (PTMs) on histones (Katada et al., 2012) to the analysis of PTMs on a proteome wide level. The extensive analysis of circadian changes of metabolites done in the Sassone-Corsi lab allowed us to relate these changes with global changes in PTMs. During the last two funding periods, we established an analysis pipeline for the investigation of lysine acetylations during the circadian cycle, and used this platform to investigate the effects of the levels of AcCoA on the global acetylome (Masri et al., 2013; Sahar et al., 2014). Moreover, we also optimized the histone modification analysis techniques such that we could investigate changes of histone PTMs in distinct areas of the brain upon a tissue specific knock-down of the dopaminergic receptor D2 autoreceptor (Brami-Cherrier et al., 2014). The platform was further extended to analyse lysine and arginine methylations using heavy methyl SILAC labelling, which is currently analysed in a systematic manner. The BaCaTeC funding allowed the establishment of a strong and reliable collaboration between the University of California Irvine and the LMU Munich, which is not only reflected by the number of publications that resulted from the work, but also by the application for an ITN within the 7th framework program of European research funding involving groups from the LMU and the group of Paolo Sassone-Corsi. Prof. Imhof has become an external faculty member at the UCI and a Memorandum of Understanding has been signed by the UCI and the LMU to foster further student exchange programs in the future.


Brami-Cherrier, K., Anzalone, A., Ramos, M., Forne, I., Macciardi, F., Imhof, A., and Borrelli, E. (2014). Epigenetic reprogramming of cortical neurons through alteration of dopaminergic circuits. Mol Psychiatry.
Katada, S., Imhof, A., and Sassone-Corsi, P. (2012). Connecting Threads: Epigenetics and Metabolism. Cell 148, 24–28.
Masri, S., Patel, V.R., Eckel-Mahan, K.L., Peleg, S., Forne, I., Ladurner, A.G., Baldi, P., Imhof, A., and Sassone-Corsi, P. (2013). Circadian acetylome reveals regulation of mitochondrial metabolic pathways. Proceedings of the National Academy of Sciences.
Sahar, S., Masubuchi, S., Eckel-Mahan, K., Vollmer, S., Galla, L., Ceglia, N., Masri, S., Barth, T.K., Grimaldi, B., Oluyemi, O., et al. (2014). Circadian Control of Fatty Acid Elongation by SIRT1-mediated Deacetylation of Acetyl-CoA Synthetase 1. Journal of Biological Chemistry jbc.M113.537191.


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