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

BMC Genomics

Research Article

Holger Klein¹  Marcel H Schulz¹  Martin Vingron¹  Stefan Roepcke²  Lars Theobald³  Sabrina Gohlke³  Diego J Walther³  Silke Stahlberg⁴ 

[1] Department of Computational Molecular Biology, Max Planck Institute for Molecular Genetics, Berlin, Germany;Department of Computational Molecular Biology, Max Planck Institute for Molecular Genetics, Berlin, Germany;Nycomed GmbH, Konstanz, Germany;Department of Human Molecular Genetics, Max Planck Institute for Molecular Genetics, Berlin, Germany;Department of Human Molecular Genetics, Max Planck Institute for Molecular Genetics, Berlin, Germany;Department of Biology, Chemistry, and Pharmacy, Free University Berlin, 14195, Berlin, Germany;

关键词: NonO;    HEK293 Cell;    Transcription Start Site;    Nuclear Extract;    Translational Apparatus;   

DOI  :  10.1186/1471-2164-12-624

 received in 2011-06-28, accepted in 2011-12-20,  发布年份 2011

来源: Springer

【 摘 要 】

BackgroundBioinformatic 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.ResultsGenome-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.ConclusionsOur 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.

【 授权许可】

Unknown   
© Roepcke et al; licensee BioMed Central Ltd. 2011. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.