Epigenetic Regulation of Monocyte and Macrophage Function

Significance: Monocytes and macrophages are key players in tissue homeostasis and immune responses. Epigenetic processes tightly regulate cellular functioning in health and disease. Recent Advances: Recent technical developments have allowed detailed characterizations of the transcriptional circuitry underlying monocyte and macrophage regulation. Upon differentiation and activation, enhancers are selected by lineage-determining and signal-dependent transcription factors. Enhancers are shown to be very dynamic and activation of these enhancers underlies the differences in gene transcription between monocytes and macrophages and their subtypes. Critical Issues: It has been shown that epigenetic enzymes regulate the functioning of these cells and targeting of epigenetic enzymes has been proven to be a valuable tool to dampen inflammatory responses. We give a comprehensive overview of recent developments and understanding of the epigenetic pathways that control monocyte and macrophage function and of the epigenetic enzymes involved in monocyte and macrophage differentiation and activation. Future Directions: The key challenges in the upcoming years will be to study epigenetic changes in human disease and to better understand how epigenetic pathways control the inflammatory repertoire in disease.