Macrophage Activation as a Model System for Understanding Enhancer Transcription and eRNA Function

Abstract

Macrophages are innate immune cells that sense the presence of pathogens through conserved pattern recognition receptors, which include TLR4. Activation of TLR4 by bacterial lipopolysaccharide induces the expression of thousands of genes that function to initiate infl ammation and coordinate innate and adaptive immune responses. Transcriptional activation of TLR4-responsive genes is mediated by signal-dependent transcription factors, such as NFκB, which bind to DNA regulatory elements termed enhancers. Recent fi ndings indicate that macrophage enhancers are actively transcribed in concert with nearby genes. Similar observations have been reported for other cell types, raising the general question of whether enhancer transcription and/or the resulting enhancer RNAs (eRNAs) are of functional importance. Here, we review the use of macrophage activation as an experimental system for addressing these questions and highlight areas for future research.