Exploiting genomics and natural genetic variation to decode macrophage enhancers

Trends Immunol. 2015 Sep;36(9):507-18. doi: 10.1016/j.it.2015.07.006. Epub 2015 Aug 19.


The mammalian genome contains on the order of a million enhancer-like regions that are required to establish the identities and functions of specific cell types. Here, we review recent studies in immune cells that have provided insight into the mechanisms that selectively activate certain enhancers in response to cell lineage and environmental signals. We describe a working model wherein distinct classes of transcription factors define the repertoire of active enhancers in macrophages through collaborative and hierarchical interactions, and discuss important challenges to this model, specifically providing examples from T cells. We conclude by discussing the use of natural genetic variation as a powerful approach for decoding transcription factor combinations that play dominant roles in establishing the enhancer landscapes, and the potential that these insights have for advancing our understanding of the molecular causes of human disease.

Publication types

  • Review

MeSH terms

  • Animals
  • Cell Lineage / genetics
  • Chromatin Assembly and Disassembly
  • Enhancer Elements, Genetic*
  • Gene Expression Regulation
  • Gene Regulatory Networks
  • Genetic Variation*
  • Genomics* / methods
  • Humans
  • Macrophages / immunology
  • Macrophages / metabolism*
  • Organ Specificity / genetics
  • Promoter Regions, Genetic
  • Transcription Factors / metabolism
  • Transcription, Genetic


  • Transcription Factors