Chromatin as a sensor of metabolic changes during early development

Abstract

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.

Molecular mechanisms of cellular metabolic homeostasis in stem cells

“… 10 In addition, metabolic intermediates can modulate epigenetic and gene expression via the regulation of chromatin-modifying enzymes, ultimately affecting cell fate. 11 These interactions form a complex network that greatly influences stem cell metabolic homeostasis.…”

Metabolic rewiring underpins human trophoblast induction

“…Overall, the analysis reveals the presence of a metabolic asymmetry in the TCA cycle between the hiTSC and nESC, with significant accumulation of α-KG in hiTSC. The latter metabolite is of interest because it can directly modulate the activity of multiple chromatin-modifying enzymes 8 . To assess whether metabolic rewiring also takes place during in vivo TE induction, we extracted median expression of all TCA cycle enzymes from published single cell RNA-sequencing (scRNA-seq) datasets 9 .…”

“…Metabolites of the TCA cycle are not only involved in energy and biomass production but can also directly affect the activity of signalling pathways and chromatin modifiers 8 . Indeed, αKG is directly involved in histone and DNA demethylation 13,14 .…”