title: Genome-wide evidence for an essential role of the human Staf/ZNF143 transcription factor in bidirectional transcription.
abstract: 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.
authors.affiliation: Department of Structural Biology and Genomics, Institut de Génétique et de Biologie Moléculaire et Cellulaire, The Centre National de la Recherche Scientifique, UMR7104, F-67400 Illkirch, France.
authors.forename: Yannick-Noël
authors.initials: YN
authors.lastname: Anno
authors.forename: Evelyne
authors.initials: E
authors.lastname: Myslinski
authors.forename: Richard Patryk
authors.initials: RP
authors.lastname: Ngondo-Mbongo
authors.forename: Alain
authors.initials: A
authors.lastname: Krol
authors.forename: Olivier
authors.initials: O
authors.lastname: Poch
authors.forename: Odile
authors.initials: O
authors.lastname: Lecompte
authors.forename: Philippe
authors.initials: P
authors.lastname: Carbon
mesh_terms: D001665:Binding Sites; D004247:DNA / Q000737:chemistry; D015536:Down-Regulation; D055785:Gene Knockdown Techniques; D015894:Genome, Human; D006367:HeLa Cells; D006801:Humans; D011401:Promoter Regions, Genetic; D011506:Proteins / Q000235:genetics; D012342:RNA, Small Nuclear / Q000235:genetics / Q000378:metabolism; D017422:Sequence Analysis, DNA; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014158:Transcription, Genetic
chemical_list: D011506:Proteins; D012342:RNA, Small Nuclear; D015534:Trans-Activators; C114253:ZNF143 protein, human; D004247:DNA