Our research activities particularly aim at studying the effects on gene expression of the multiple PTMs that target histone lysine residues. In particular, various acylations have been described since 2007, which resemble acetylation, yet differ in length, hydrophobicity and charge, and emerge as being endowed with specific functions compared to acetylation. All these acylations connect the histone PTM profile to cellular metabolites, more precisely to acyls-CoA (e.g. acetyl-CoA, crotonyl-CoA, etc.) and to the corresponding carboxylates (acetate, crotonate, etc.). We have carried out such explorations in the context of mouse spermatogenesis [7,9]. In particular, the proteomic analysis of histones extracted from three cellular stages of mouse spermatogenesis revealed that crotonylation was of similar stoichiometry to acetylation on histone H3 Lysine 27 (H3K27cr). Epigenomic analyses of H3K27cr and of the canonical mark H3K27ac indicated both synergistic and specific actions of each histone modification at promoters and distal enhancers [7]. We are pursuing our efforts to characterize further acylations in mouse spermatogenesis, including the more recently described lactylation.

Over the last years, we have expanded the study of histone lysine acylations to pathologies in which epigenetic landscapes are rewired. In particular, we contribute to deciphering the links between dysregulated metabolism and revisited histone PTM profiles in Huntington’s disease (HD), a rare genetic neurodegenerative disease that primarily affects the striatum. To achieve this goal, we have established isotope tracing which allows following the kinetics of histone acetylation at multiple lysine residues after injection into mice of a heavy labeled metabolite such as glucose.

Over the next years, we wish to reinforce this research axis aiming at deciphering the links between imbalanced metabolism and epigenetic dysregulations, in particular in neurodegenerative diseases.