Epigenomic regulation by labile iron

Iron is an essential micronutrient metal for cellular functions but can generate highly reactive oxygen species resulting in oxidative damage. For these reasons its uptake and metabolism is highly regulated. A small but dynamic fraction of ferrous iron inside the cell, termed intracellular labile iron, is redox-reactive and ready to participate multiples reactions of intracellular enzymes. Due to its nature its determination and precise quantification has been a roadblock. However, recent progress in the development of intracellular labile iron probes are allowing the reevaluation of our current understanding and unmasking new functions. The role of intracellular labile iron in regulating the epigenome was recently discovered. This chapter examine how intracellular labile iron can modulate histone and DNA demethylation and how its pool can mediate a signaling pathway from cAMP serving as a sensor of the metabolic needs of the cells. [Display omitted] •Labile Fe(II) is redox-reactive, dynamic and required for enzymatic reactions.•Labile Fe(II), as an essential cofactor, is involved in the demethylation of DNA and histones.•Diseases that alter the intracellular labile Fe(II) pool can affect the epigenome.•cAMP signaling promotes DNA and histone demethylation by increasing intracellular labile Fe(II) pool.