Bidirectional Transcription Arises from Two Distinct Hubs of Transcription Factor Binding and Active Chromatin

Mol Cell. 2015 Jun 18;58(6):1101-12. doi: 10.1016/j.molcel.2015.04.006. Epub 2015 May 28.


Anti-sense transcription originating upstream of mammalian protein-coding genes is a well-documented phenomenon, but remarkably little is known about the regulation or function of anti-sense promoters and the non-coding RNAs they generate. Here we define at nucleotide resolution the divergent transcription start sites (TSSs) near mouse mRNA genes. We find that coupled sense and anti-sense TSSs precisely define the boundaries of a nucleosome-depleted region (NDR) that is highly enriched in transcription factor (TF) motifs. Notably, as the distance between sense and anti-sense TSSs increases, so does the size of the NDR, the level of signal-dependent TF binding, and gene activation. We further discover a group of anti-sense TSSs in macrophages with an enhancer-like chromatin signature. Interestingly, this signature identifies divergent promoters that are activated during immune challenge. We propose that anti-sense promoters serve as platforms for TF binding and establishment of active chromatin to further regulate or enhance sense-strand mRNA expression.

Publication types

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

MeSH terms

  • Animals
  • Base Sequence
  • Binding Sites
  • Cells, Cultured
  • Chromatin / genetics*
  • Chromatin / metabolism
  • DNA, Antisense / genetics
  • Gene Expression Regulation
  • Macrophages / metabolism
  • Mice, Inbred C57BL
  • Models, Genetic
  • Nucleosomes / genetics
  • Nucleosomes / metabolism
  • Nucleotide Motifs / genetics
  • Promoter Regions, Genetic / genetics
  • Protein Binding
  • RNA, Messenger / genetics
  • Transcription Factors / metabolism*
  • Transcription Initiation Site*
  • Transcription, Genetic*


  • Chromatin
  • DNA, Antisense
  • Nucleosomes
  • RNA, Messenger
  • Transcription Factors

Associated data

  • GEO/GSE62151