Crosstalk between NUAK1 and the SETD1A complex regulates glycolysis and gluconeogenesis upon glucose deprivation

Importantly, these metabolites are substrates for chromatin modifications. We previously found that increases in the levels of histone H3T11 phosphorylation (H3pT11) upon limited nutrition changes the profiles of gene expression in yeast.

However, it remains unclear how human cells respond to nutritional stress and whether transcriptional regulation associated with H3T11p contributes to the nutritional stress response in humans. Here, we studied how gene expression was regulated in response to glucose deprivation in human cells. We found that interactions of the NUAK family kinase 1 (NUAK1) with the histone H3K4 methyltransferase, SETD1A, play a critical role in response to glucose starvation by controlling the expression of metabolic enzymes, including Hexokinase 2 and phosphoenolpyruvate carboxykinase 2.