Epigenetic control of myeloid cell differentiation, identity and function

The interplay between transcription factors and epigenetic regulators is crucial for regulating gene-expression programmes during haematopoiesis. Epigenetic regulation — including post-translational modification of histones and DNA methylation — is also linked with upstream signalling pathways and external signals that shape the identity and function of immune cells.Distinctive DNA methylation changes characterize the differentiation of myeloid cells and lymphoid cells from their progenitors. DNA demethylation is more predominant during myeloid differentiation than during lymphoid differentiation.The methylcytosine hydroxylase TET2, which oxidizes 5-methylcytosine, has a major role in the acquisition of myeloid cell identity. This has been demonstrated using transdifferentiation models and is highlighted by the association of TET2 mutations with myeloid malignancies.Epigenetic control has a key role in defining macrophage polarization, connecting external stimuli with the establishment of specific transcriptional programmes.Epigenetic modifications have a key role in the generation of memory-type behaviour in innate immune cells. Following an initial stimulus, the persistence of the trimethylated histone H3K4 at latent enhancers ensures the increased expression of pro-inflammatory genes after restimulation.