Integrative Analysis Unveils the Correlation of Aminoacyl-tRNA Biosynthesis Metabolites with the Methylation of the SEPSECS Gene in Huntington's Disease Brain Tissue.

The impact of environmental factors on epigenetic changes is well established, and cellular function is determined not only by the genome but also by interacting partners such as metabolites. Given the significant impact of metabolism on disease progression, exploring the interaction between the metabolome and epigenome may offer new insights into Huntington's disease (HD) diagnosis and treatment. Using fourteen post-mortem HD cases and fourteen control subjects, we performed metabolomic profiling of human postmortem brain tissue (striatum and frontal lobe), and we performed DNA methylome profiling using the same frontal lobe tissue. Along with finding several perturbed metabolites and differentially methylated loci, Aminoacyl-tRNA biosynthesis (adj p-value = 0.0098) was the most significantly perturbed metabolic pathway with which two CpGs of the SEPSECS gene were correlated. This study improves our understanding of molecular biomarker connections and, importantly, increases our knowledge of metabolic alterations driving HD progression.

Chromatin as a sensor of metabolic changes during early development.

Cellular metabolism is a complex network of biochemical reactions fueling development with energy and biomass; however, it can also shape the cellular epigenome. Indeed, some intermediates of metabolic reactions exert a non-canonical function by acting as co-factors, substrates or inhibitors of chromatin modifying enzymes. Therefore, fluctuating availability of such molecules has the potential to regulate the epigenetic landscape. Thanks to this functional coupling, chromatin can act as a sensor of metabolic changes and thus impact cell fate. Growing evidence suggest that both metabolic and epigenetic reprogramming are crucial for ensuring a successful embryo development from the zygote until gastrulation. In this review, we provide an overview of the complex relationship between metabolism and epigenetics in regulating the early stages of mammalian embryo development. We report on recent breakthroughs in uncovering the non-canonical functions of metabolism especially when re-localized to the nucleus. In addition, we identify the challenges and outline future perspectives to advance the novel field of epi-metabolomics especially in the context of early development.