Histone-fold domain protein NF-Y promotes chromatin accessibility for cell type-specific master transcription factors

Mol Cell. 2014 Sep 4;55(5):708-22. doi: 10.1016/j.molcel.2014.07.005. Epub 2014 Aug 14.


Cell type-specific master transcription factors (TFs) play vital roles in defining cell identity and function. However, the roles ubiquitous factors play in the specification of cell identity remain underappreciated. Here we show that the ubiquitous CCAAT-binding NF-Y complex is required for the maintenance of embryonic stem cell (ESC) identity and is an essential component of the core pluripotency network. Genome-wide studies in ESCs and neurons reveal that NF-Y regulates not only genes with housekeeping functions through cell type-invariant promoter-proximal binding, but also genes required for cell identity by binding to cell type-specific enhancers with master TFs. Mechanistically, NF-Y's distinct DNA-binding mode promotes master/pioneer TF binding at enhancers by facilitating a permissive chromatin conformation. Our studies unearth a conceptually unique function for histone-fold domain (HFD) protein NF-Y in promoting chromatin accessibility and suggest that other HFD proteins with analogous structural and DNA-binding properties may function in similar ways.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Binding Sites
  • CCAAT-Binding Factor / metabolism
  • CCAAT-Binding Factor / physiology*
  • Cells, Cultured
  • Chromatin / metabolism*
  • Embryonic Stem Cells / metabolism
  • Embryonic Stem Cells / ultrastructure
  • Histones / metabolism*
  • Mice
  • Models, Genetic
  • Nucleosomes / chemistry
  • Nucleosomes / metabolism
  • Pluripotent Stem Cells
  • Transcription Factors / chemistry
  • Transcription Factors / metabolism
  • Transcription Factors / physiology


  • CCAAT-Binding Factor
  • Chromatin
  • Histones
  • Nucleosomes
  • Transcription Factors

Associated data

  • GEO/GSE56840