NF-Y controls fidelity of transcription initiation at gene promoters through maintenance of the nucleosome-depleted region

Nat Commun. 2019 Jul 11;10(1):3072. doi: 10.1038/s41467-019-10905-7.


Faithful transcription initiation is critical for accurate gene expression, yet the mechanisms underlying specific transcription start site (TSS) selection in mammals remain unclear. Here, we show that the histone-fold domain protein NF-Y, a ubiquitously expressed transcription factor, controls the fidelity of transcription initiation at gene promoters in mouse embryonic stem cells. We report that NF-Y maintains the region upstream of TSSs in a nucleosome-depleted state while simultaneously protecting this accessible region against aberrant and/or ectopic transcription initiation. We find that loss of NF-Y binding in mammalian cells disrupts the promoter chromatin landscape, leading to nucleosomal encroachment over the canonical TSS. Importantly, this chromatin rearrangement is accompanied by upstream relocation of the transcription pre-initiation complex and ectopic transcription initiation. Further, this phenomenon generates aberrant extended transcripts that undergo translation, disrupting gene expression profiles. These results suggest NF-Y is a central player in TSS selection in metazoans and highlight the deleterious consequences of inaccurate transcription initiation.

Publication types

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

MeSH terms

  • Animals
  • CCAAT-Binding Factor / genetics
  • CCAAT-Binding Factor / metabolism*
  • Cell Line
  • Chromatin / genetics
  • Chromatin / metabolism
  • Embryonic Stem Cells
  • Gene Knockdown Techniques
  • Mice
  • Nucleosomes / genetics
  • Nucleosomes / metabolism*
  • Promoter Regions, Genetic / genetics
  • RNA, Small Interfering / metabolism
  • Transcription Initiation Site*
  • Transcription Initiation, Genetic*


  • CCAAT-Binding Factor
  • Chromatin
  • Nfya protein, mouse
  • Nucleosomes
  • RNA, Small Interfering