NF-Y coassociates with FOS at promoters, enhancers, repetitive elements, and inactive chromatin regions, and is stereo-positioned with growth-controlling transcription factors

Genome Res. 2013 Aug;23(8):1195-209. doi: 10.1101/gr.148080.112. Epub 2013 Apr 17.


NF-Y, a trimeric transcription factor (TF) composed of two histone-like subunits (NF-YB and NF-YC) and a sequence-specific subunit (NF-YA), binds to the CCAAT motif, a common promoter element. Genome-wide mapping reveals 5000-15,000 NF-Y binding sites depending on the cell type, with the NF-YA and NF-YB subunits binding asymmetrically with respect to the CCAAT motif. Despite being characterized as a proximal promoter TF, only 25% of NF-Y sites map to promoters. A comparable number of NF-Y sites are located at enhancers, many of which are tissue specific, and nearly half of the NF-Y sites are in select subclasses of HERV LTR repeats. Unlike most TFs, NF-Y can access its target DNA motif in inactive (nonmodified) or polycomb-repressed chromatin domains. Unexpectedly, NF-Y extensively colocalizes with FOS in all genomic contexts, and this often occurs in the absence of JUN and the AP-1 motif. NF-Y also coassociates with a select cluster of growth-controlling and oncogenic TFs, consistent with the abundance of CCAAT motifs in the promoters of genes overexpressed in cancer. Interestingly, NF-Y and several growth-controlling TFs bind in a stereo-specific manner, suggesting a mechanism for cooperative action at promoters and enhancers. Our results indicate that NF-Y is not merely a commonly used proximal promoter TF, but rather performs a more diverse set of biological functions, many of which are likely to involve coassociation with FOS.

Publication types

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

MeSH terms

  • Base Sequence
  • Binding Sites
  • CCAAT-Binding Factor / metabolism*
  • Chromatin / genetics
  • Chromatin / metabolism
  • Consensus Sequence
  • Enhancer Elements, Genetic*
  • Gene Expression Regulation
  • Gene Ontology
  • Genome, Human
  • HeLa Cells
  • Humans
  • K562 Cells
  • Molecular Sequence Annotation
  • Organ Specificity
  • Promoter Regions, Genetic*
  • Protein Binding
  • Protein Transport
  • Proto-Oncogene Proteins c-fos / metabolism*
  • Terminal Repeat Sequences
  • Transcription Factors / metabolism
  • Transcription Initiation Site


  • CCAAT-Binding Factor
  • Chromatin
  • NFYA protein, human
  • NFYB protein, human
  • Proto-Oncogene Proteins c-fos
  • Transcription Factors

Associated data

  • GEO/GSE40215