Genetic determinants and epigenetic effects of pioneer-factor occupancy

Nat Genet. 2018 Feb;50(2):250-258. doi: 10.1038/s41588-017-0034-3. Epub 2018 Jan 22.


Transcription factors (TFs) direct developmental transitions by binding to target DNA sequences, influencing gene expression and establishing complex gene-regultory networks. To systematically determine the molecular components that enable or constrain TF activity, we investigated the genomic occupancy of FOXA2, GATA4 and OCT4 in several cell types. Despite their classification as pioneer factors, all three TFs exhibit cell-type-specific binding, even when supraphysiologically and ectopically expressed. However, FOXA2 and GATA4 can be distinguished by low enrichment at loci that are highly occupied by these factors in alternative cell types. We find that expression of additional cofactors increases enrichment at a subset of these sites. Finally, FOXA2 occupancy and changes to DNA accessibility can occur in G1-arrested cells, but subsequent loss of DNA methylation requires DNA replication.

Publication types

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

MeSH terms

  • A549 Cells
  • Binding Sites / genetics
  • Cell Lineage / drug effects
  • Cell Lineage / genetics
  • Cells, Cultured
  • Computational Biology
  • DNA / genetics
  • DNA / metabolism*
  • Epigenesis, Genetic / physiology*
  • Epistasis, Genetic / physiology
  • GATA4 Transcription Factor / metabolism
  • Gene Expression Regulation
  • Gene Regulatory Networks / physiology*
  • Genes, Switch
  • HEK293 Cells
  • Hep G2 Cells
  • Hepatocyte Nuclear Factor 3-beta / metabolism
  • Humans
  • Octamer Transcription Factor-3 / metabolism
  • Protein Binding
  • Transcription Factors / metabolism*


  • FOXA2 protein, human
  • GATA4 Transcription Factor
  • GATA4 protein, human
  • Octamer Transcription Factor-3
  • POU5F1 protein, human
  • Transcription Factors
  • Hepatocyte Nuclear Factor 3-beta
  • DNA