Fig. 1.

Cross-regulation of metabolism and chromatin that control HSPC function. a Metabolic reactions use precursors and produce metabolites, some of which are (a) genotoxic and damage DNA, and some of which can directly regulate (enhance or inhibit) the activities of chromatin modulators in modifying DNA and/or histones and remodeling nucleosomes. b DNA damage is also suggested to cause increased ROS. c Changes in the chromatin state at the damaged DNA sites can directly influence the sensing and repair of the damage. d Chromatin changes also activate or repress transcription and expression of genes encoding key metabolic enzymes, cell fate regulators, and DDR factors that participate in DDR, which together influence the function and fate determination of cells in different lineages, including HSPCs. b Examples of metabolites that inhibit (in red) or promote (in green) the corresponding chromatin enzymes