Genome-wide evidence for an essential role of the human Staf/ZNF143 transcription factor in bidirectional transcription

Nucleic Acids Res. 2011 Apr;39(8):3116-27. doi: 10.1093/nar/gkq1301. Epub 2010 Dec 21.


In the human genome, ∼ 10% of the genes are arranged head to head so that their transcription start sites reside within <1 kbp on opposite strands. In this configuration, a bidirectional promoter generally drives expression of the two genes. How bidirectional expression is performed from these particular promoters constitutes a puzzling question. Here, by a combination of in silico and biochemical approaches, we demonstrate that hStaf/ZNF143 is involved in controlling expression from a subset of divergent gene pairs. The binding sites for hStaf/ZNF143 (SBS) are overrepresented in bidirectional versus unidirectional promoters. Chromatin immunoprecipitation assays with a significant set of bidirectional promoters containing putative SBS revealed that 93% of them are associated with hStaf/ZNF143. Expression of dual reporter genes directed by bidirectional promoters are dependent on the SBS integrity and requires hStaf/ZNF143. Furthermore, in some cases, functional SBS are located in bidirectional promoters of gene pairs encoding a noncoding RNA and a protein gene. Remarkably, hStaf/ZNF143 per se exhibits an inherently bidirectional transcription activity, and together our data provide the demonstration that hStaf/ZNF143 is indeed a transcription factor controlling the expression of divergent protein-protein and protein-non-coding RNA gene pairs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • DNA / chemistry
  • Down-Regulation
  • Gene Knockdown Techniques
  • Genome, Human
  • HeLa Cells
  • Humans
  • Promoter Regions, Genetic*
  • Proteins / genetics
  • RNA, Small Nuclear / genetics
  • RNA, Small Nuclear / metabolism
  • Sequence Analysis, DNA
  • Trans-Activators / genetics
  • Trans-Activators / metabolism
  • Trans-Activators / physiology*
  • Transcription, Genetic*


  • Proteins
  • RNA, Small Nuclear
  • Trans-Activators
  • ZNF143 protein, human
  • DNA