FoxA1 translates epigenetic signatures into enhancer-driven lineage-specific transcription

Cell. 2008 Mar 21;132(6):958-70. doi: 10.1016/j.cell.2008.01.018.


Complex organisms require tissue-specific transcriptional programs, yet little is known about how these are established. The transcription factor FoxA1 is thought to contribute to gene regulation through its ability to act as a pioneer factor binding to nucleosomal DNA. Through genome-wide positional analyses, we demonstrate that FoxA1 cell type-specific functions rely primarily on differential recruitment to chromatin predominantly at distant enhancers rather than proximal promoters. This differential recruitment leads to cell type-specific changes in chromatin structure and functional collaboration with lineage-specific transcription factors. Despite the ability of FoxA1 to bind nucleosomes, its differential binding to chromatin sites is dependent on the distribution of histone H3 lysine 4 dimethylation. Together, our results suggest that methylation of histone H3 lysine 4 is part of the epigenetic signature that defines lineage-specific FoxA1 recruitment sites in chromatin. FoxA1 translates this epigenetic signature into changes in chromatin structure thereby establishing lineage-specific transcriptional enhancers and programs.

Publication types

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

MeSH terms

  • Cell Line, Tumor
  • Chromatin Assembly and Disassembly
  • Chromatin Immunoprecipitation
  • Enhancer Elements, Genetic*
  • Epigenesis, Genetic*
  • Estrogen Receptor alpha / metabolism
  • Estrogens / metabolism
  • Genome, Human
  • Hepatocyte Nuclear Factor 3-alpha / metabolism*
  • Histone Code
  • Histones / metabolism
  • Humans
  • Methylation
  • Receptors, Androgen / metabolism
  • Transcription, Genetic*


  • Estrogen Receptor alpha
  • Estrogens
  • FOXA1 protein, human
  • Hepatocyte Nuclear Factor 3-alpha
  • Histones
  • Receptors, Androgen