Epigenetic control of myeloid cell differentiation, identity and function

Abstract

Myeloid cells are crucial effectors of the innate immune response and important regulators of adaptive immunity. The differentiation and activation of myeloid cells requires the timely regulation of gene expression; this depends on the interplay of a variety of elements, including transcription factors and epigenetic mechanisms. Epigenetic control involves histone modifications and DNA methylation, and is coupled to lineage-specifying transcription factors, upstream signalling pathways and external factors released in the bone marrow, blood and tissue environments. In this Review, we highlight key epigenetic events controlling myeloid cell biology, focusing on those related to myeloid cell differentiation, the acquisition of myeloid identity and innate immune memory.

Reprogramming of histone methylation controls the differentiation of monocytes into macrophages

“…Furthermore, genetic deficiency of EZH2 increases natural killer (NK) cell lineage commitment and differentiation in vivo [11]. These findings suggest that immune cell differentiation depends on stage-and lineage-specific epigenetic regulators, such as PcG, which determine genome-wide expression patterns in precursors [12,13]. The mixed-lineage leukemia proteins (MLL) are orthologs of TrxG genes that functionally antagonize PcG [8].…”

'Trained immunity: consequences for lymphoid malignancies

“…[16][17][18][19] Several mechanisms are involved in the development of innate immune memory, among which epigenetic histone modifications (e.g., histone methylation and acetylation), and autophagy play a central role. Monocytes are functionally reprogrammed for either enhanced (training) or decreased (tolerance) cytokine production, depending on the type and concentration of MAMPs they encountered 17,[20][21][22] ( Figure 1). The epigenetic reprogramming of monocytes after MAMP stimulation results in functional as well as morphological changes, including cell surface marker modifications such as upregulation of TLR expression.…”

Signatures of DNA target selectivity by ETS transcription factors

“…While the importance of epigenetic regulation of ETSdependent transcription is well established in hematopoiesis and cancer, 55,[66][67][68] the mechanisms by which ETS activity are modulated at epigenetically modified DNA, with or without nucleosome, are not well understood. Genomic surveys have found that hematopoietic ETS transcription factors are over-represented in hypermethylated regions.…”