View the Current Issue

Article

  • The EMBO Journal (2007) 26, 944 - 954
  • doi:10.1038/sj.emboj.7601550

Published online: 1 February 2007

Identification of novel functional TBP-binding sites and general factor repertoires

Sergey Denissov1, Marc van Driel1,2, Renate Voit3, Maarten Hekkelman2, Tim Hulsen2, Nouria Hernandez4,a, Ingrid Grummt3, Ron Wehrens5 and Hendrik Stunnenberg1

  1. Department of Molecular Biology, Nijmegen Centre for Molecular Life Sciences, Radboud University, Nijmegen, The Netherlands
  2. Centre for Molecular and Biomolecular Informatics, Radboud University, Nijmegen, The Netherlands
  3. Division of Molecular Biology of the Cell II, German Cancer Research Center, Heidelberg, Germany
  4. Howard Hughes Medical Institute, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, USA
  5. Institute for Molecules and Materials, Radboud University, Nijmegen, The Netherlands

Correspondence to:

Hendrik Stunnenberg, Department of Molecular Biology, Nijmegen Centre for Molecular Life Sciences (274), Radboud University, PO Box 9101 6500, HB Nijmegen, The Netherlands. Tel.: +31 24 3610524; Fax: +31 24 3610520; E-mail: h.stunnenberg@ncmls.ru.nl

aPresent address: Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland

Received 26 June 2006; Accepted 15 December 2006

Our current knowledge of the general factor requirement in transcription by the three mammalian RNA polymerases is based on a small number of model promoters. Here, we present a comprehensive chromatin immunoprecipitation (ChIP)-on-chip analysis for 28 transcription factors on a large set of known and novel TATA-binding protein (TBP)-binding sites experimentally identified via ChIP cloning. A large fraction of identified TBP-binding sites is located in introns or lacks a gene/mRNA annotation and is found to direct transcription. Integrated analysis of the ChIP-on-chip data and functional studies revealed that TAF12 hitherto regarded as RNA polymerase II (RNAP II)-specific was found to be also involved in RNAP I transcription. Distinct profiles for general transcription factors and TAF-containing complexes were uncovered for RNAP II promoters located in CpG and non-CpG islands suggesting distinct transcription initiation pathways. Our study broadens the spectrum of general transcription factor function and uncovers a plethora of novel, functional TBP-binding sites in the human genome.

  • Keywords:

    • ChIP-on-chip,
    • promoter,
    • TBP,
    • transcription factor profiling