Epigenetic program and transcription factor circuitry of dendritic cell development

Nucleic Acids Res. 2015 Nov 16;43(20):9680-93. doi: 10.1093/nar/gkv1056. Epub 2015 Oct 17.


Dendritic cells (DC) are professional antigen presenting cells that develop from hematopoietic stem cells through successive steps of lineage commitment and differentiation. Multipotent progenitors (MPP) are committed to DC restricted common DC progenitors (CDP), which differentiate into specific DC subsets, classical DC (cDC) and plasmacytoid DC (pDC). To determine epigenetic states and regulatory circuitries during DC differentiation, we measured consecutive changes of genome-wide gene expression, histone modification and transcription factor occupancy during the sequel MPP-CDP-cDC/pDC. Specific histone marks in CDP reveal a DC-primed epigenetic signature, which is maintained and reinforced during DC differentiation. Epigenetic marks and transcription factor PU.1 occupancy increasingly coincide upon DC differentiation. By integrating PU.1 occupancy and gene expression we devised a transcription factor regulatory circuitry for DC commitment and subset specification. The circuitry provides the transcription factor hierarchy that drives the sequel MPP-CDP-cDC/pDC, including Irf4, Irf8, Tcf4, Spib and Stat factors. The circuitry also includes feedback loops inferred for individual or multiple factors, which stabilize distinct stages of DC development and DC subsets. In summary, here we describe the basic regulatory circuitry of transcription factors that drives DC development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Lineage
  • Cells, Cultured
  • Dendritic Cells / metabolism*
  • Epigenesis, Genetic*
  • Gene Regulatory Networks*
  • Hematopoietic Stem Cells / metabolism
  • Histones / metabolism
  • Mice
  • Proto-Oncogene Proteins / metabolism
  • Trans-Activators / metabolism
  • Transcription Factors / metabolism*


  • Histones
  • Proto-Oncogene Proteins
  • Trans-Activators
  • Transcription Factors
  • proto-oncogene protein Spi-1