Lineage-specific enhancers activate self-renewal genes in macrophages and embryonic stem cells

Science. 2016 Feb 12;351(6274):aad5510. doi: 10.1126/science.aad5510. Epub 2016 Jan 21.


Differentiated macrophages can self-renew in tissues and expand long term in culture, but the gene regulatory mechanisms that accomplish self-renewal in the differentiated state have remained unknown. Here we show that in mice, the transcription factors MafB and c-Maf repress a macrophage-specific enhancer repertoire associated with a gene network that controls self-renewal. Single-cell analysis revealed that, in vivo, proliferating resident macrophages can access this network by transient down-regulation of Maf transcription factors. The network also controls embryonic stem cell self-renewal but is associated with distinct embryonic stem cell-specific enhancers. This indicates that distinct lineage-specific enhancer platforms regulate a shared network of genes that control self-renewal potential in both stem and mature cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / genetics*
  • Cell Lineage / genetics*
  • Cell Proliferation
  • Cells, Cultured
  • Down-Regulation
  • Embryonic Stem Cells / cytology*
  • Enhancer Elements, Genetic / physiology*
  • Gene Expression Regulation*
  • Gene Regulatory Networks
  • Macrophages / cytology*
  • MafB Transcription Factor / metabolism
  • Mice
  • Proto-Oncogene Proteins c-maf / metabolism
  • Single-Cell Analysis
  • Transcriptional Activation


  • Maf protein, mouse
  • MafB Transcription Factor
  • Mafb protein, mouse
  • Proto-Oncogene Proteins c-maf