title: A tandem sequence motif acts as a distance-dependent enhancer in a set of genes involved in translation by binding the proteins NonO and SFPQ.
abstract: BACKGROUND
  Bioinformatic analyses of expression control sequences in promoters of co-expressed or functionally related genes enable the discovery of common regulatory sequence motifs that might be involved in co-ordinated gene expression. By studying promoter sequences of the human ribosomal protein genes we recently identified a novel highly specific Localized Tandem Sequence Motif (LTSM). In this work we sought to identify additional genes and LTSM-binding proteins to elucidate potential regulatory mechanisms.
  
  
  RESULTS
  Genome-wide analyses allowed finding a considerable number of additional LTSM-positive genes, the products of which are involved in translation, among them, translation initiation and elongation factors, and 5S rRNA. Electromobility shift assays then showed specific signals demonstrating the binding of protein complexes to LTSM in ribosomal protein gene promoters. Pull-down assays with LTSM-containing oligonucleotides and subsequent mass spectrometric analysis identified the related multifunctional nucleotide binding proteins NonO and SFPQ in the binding complex. Functional characterization then revealed that LTSM enhances the transcriptional activity of the promoters in dependency of the distance from the transcription start site.
  
  
  CONCLUSIONS
  Our data demonstrate the power of bioinformatic analyses for the identification of biologically relevant sequence motifs. LTSM and the here found LTSM-binding proteins NonO and SFPQ were discovered through a synergistic combination of bioinformatic and biochemical methods and are regulators of the expression of a set of genes of the translational apparatus in a distance-dependent manner.
authors.affiliation: Department of Human Molecular Genetics, Max Planck Institute for Molecular Genetics, Berlin, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Roepcke
authors.forename: Silke
authors.initials: S
authors.lastname: Stahlberg
authors.forename: Holger
authors.initials: H
authors.lastname: Klein
authors.forename: Marcel H
authors.initials: MH
authors.lastname: Schulz
authors.forename: Lars
authors.initials: L
authors.lastname: Theobald
authors.forename: Sabrina
authors.initials: S
authors.lastname: Gohlke
authors.forename: Martin
authors.initials: M
authors.lastname: Vingron
authors.forename: Diego J
authors.initials: DJ
authors.lastname: Walther
mesh_terms: D004268:DNA-Binding Proteins; D004742:Enhancer Elements, Genetic; D006801:Humans; D034521:Nuclear Matrix-Associated Proteins / Q000378:metabolism*; D050810:Octamer Transcription Factors / Q000378:metabolism*; D000072670:PTB-Associated Splicing Factor; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D014176:Protein Biosynthesis; D016601:RNA-Binding Proteins / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; C083214:NONO protein, human; D034521:Nuclear Matrix-Associated Proteins; D050810:Octamer Transcription Factors; D000072670:PTB-Associated Splicing Factor; D016601:RNA-Binding Proteins