Genome-wide analysis of repressor element 1 silencing transcription factor/neuron-restrictive silencing factor (REST/NRSF) target genes

DOI Web Site 被引用文献22件
  • Alexander W. Bruce
    Schools of Biochemistry and Microbiology and Biomedical Sciences, University of Leeds, Leeds LS2 9JT, United Kingdom; and Cambridge Institute of Medical Research, Wellcome Trust/MRC Building, Addenbrooke's Hospital, Cambridge CB2 2XY, United Kingdom
  • Ian J. Donaldson
    Schools of Biochemistry and Microbiology and Biomedical Sciences, University of Leeds, Leeds LS2 9JT, United Kingdom; and Cambridge Institute of Medical Research, Wellcome Trust/MRC Building, Addenbrooke's Hospital, Cambridge CB2 2XY, United Kingdom
  • Ian C. Wood
    Schools of Biochemistry and Microbiology and Biomedical Sciences, University of Leeds, Leeds LS2 9JT, United Kingdom; and Cambridge Institute of Medical Research, Wellcome Trust/MRC Building, Addenbrooke's Hospital, Cambridge CB2 2XY, United Kingdom
  • Sally A. Yerbury
    Schools of Biochemistry and Microbiology and Biomedical Sciences, University of Leeds, Leeds LS2 9JT, United Kingdom; and Cambridge Institute of Medical Research, Wellcome Trust/MRC Building, Addenbrooke's Hospital, Cambridge CB2 2XY, United Kingdom
  • Michael I. Sadowski
    Schools of Biochemistry and Microbiology and Biomedical Sciences, University of Leeds, Leeds LS2 9JT, United Kingdom; and Cambridge Institute of Medical Research, Wellcome Trust/MRC Building, Addenbrooke's Hospital, Cambridge CB2 2XY, United Kingdom
  • Michael Chapman
    Schools of Biochemistry and Microbiology and Biomedical Sciences, University of Leeds, Leeds LS2 9JT, United Kingdom; and Cambridge Institute of Medical Research, Wellcome Trust/MRC Building, Addenbrooke's Hospital, Cambridge CB2 2XY, United Kingdom
  • Berthold Göttgens
    Schools of Biochemistry and Microbiology and Biomedical Sciences, University of Leeds, Leeds LS2 9JT, United Kingdom; and Cambridge Institute of Medical Research, Wellcome Trust/MRC Building, Addenbrooke's Hospital, Cambridge CB2 2XY, United Kingdom
  • Noel J. Buckley
    Schools of Biochemistry and Microbiology and Biomedical Sciences, University of Leeds, Leeds LS2 9JT, United Kingdom; and Cambridge Institute of Medical Research, Wellcome Trust/MRC Building, Addenbrooke's Hospital, Cambridge CB2 2XY, United Kingdom

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<jats:p> The completion of whole genome sequencing projects has provided the genetic instructions of life. However, whereas the identification of gene coding regions has progressed, the mapping of transcriptional regulatory motifs has moved more slowly. To understand how distinct expression profiles can be established and maintained, a greater understanding of these sequences and their trans-acting factors is required. Herein we have used a combined <jats:italic>in silico</jats:italic> and biochemical approach to identify binding sites [repressor element 1/neuron-restrictive silencer element (RE1/NRSE)] and potential target genes of RE1 silencing transcription factor/neuron-restrictive silencing factor (REST/NRSF) within the human, mouse, and <jats:italic>Fugu rubripes</jats:italic> genomes. We have used this genome-wide analysis to identify 1,892 human, 1,894 mouse, and 554 <jats:italic>Fugu</jats:italic> RE1/NRSEs and present their location and gene linkages in a searchable database. Furthermore, we identified an <jats:italic>in vivo</jats:italic> hierarchy in which distinct subsets of RE1/NRSEs interact with endogenous levels of REST/NRSF, whereas others function as bona fide transcriptional control elements only in the presence of elevated levels of REST/NRSF. These data show that individual RE1/NRSE sites interact differentially with REST/NRSF within a particular cell type. This combined bioinformatic and biochemical approach serves to illustrate the selective manner in which a transcription factor interacts with its potential binding sites and regulates target genes. In addition, this approach provides a unique whole-genome map for a given transcription factor-binding site implicated in establishing specific patterns of neuronal gene expression. </jats:p>

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