A high definition look at the NF-Y regulome reveals genome-wide associations with selected transcription factors

Nucleic Acids Res. 2016 Jun 2;44(10):4684-702. doi: 10.1093/nar/gkw096. Epub 2016 Feb 20.


NF-Y is a trimeric transcription factor (TF), binding the CCAAT box element, for which several results suggest a pioneering role in activation of transcription. In this work, we integrated 380 ENCODE ChIP-Seq experiments for 154 TFs and cofactors with sequence analysis, protein-protein interactions and RNA profiling data, in order to identify genome-wide regulatory modules resulting from the co-association of NF-Y with other TFs. We identified three main degrees of co-association with NF-Y for sequence-specific TFs. In the most relevant one, we found TFs having a significant overlap with NF-Y in their DNA binding loci, some with a precise spacing of binding sites with respect to the CCAAT box, others (FOS, Sp1/2, RFX5, IRF3, PBX3) mostly lacking their canonical binding site and bound to arrays of well spaced CCAAT boxes. As expected, NF-Y binding also correlates with RNA Pol II General TFs and with subunits of complexes involved in the control of H3K4 methylations. Co-association patterns are confirmed by protein-protein interactions, and correspond to specific functional categorizations and expression level changes of target genes following NF-Y inactivation. These data define genome-wide rules for the organization of NF-Y-centered regulatory modules, supporting a model of distinct categorization and synergy with well defined sets of TFs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • CCAAT-Binding Factor / metabolism*
  • Cell Line
  • Chromatin Immunoprecipitation
  • DNA / chemistry
  • DNA / metabolism
  • Gene Expression Profiling
  • Genome
  • Humans
  • Promoter Regions, Genetic*
  • Protein Interaction Mapping
  • Sequence Analysis, DNA
  • Transcription Factors / metabolism*


  • CCAAT-Binding Factor
  • Transcription Factors
  • DNA