Dynamic and complex transcription factor binding during an inducible response in yeast

  1. Li Ni1,9,
  2. Can Bruce2,3,9,
  3. Christopher Hart4,
  4. Justine Leigh-Bell5,
  5. Daniel Gelperin6,
  6. Lara Umansky1,
  7. Mark B. Gerstein2,7,8 and
  8. Michael Snyder1,2,10
  1. 1Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, Connecticut 06520, USA;
  2. 2Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06520, USA;
  3. 3Keck Foundation Biotechnology Resource Laboratory, Yale University, New Haven, Connecticut 06520, USA;
  4. 4Helicos Biosciences, Cambridge, Massachusetts 02139, USA;
  5. 5Center for Regulation Genomics, Barcelona, Spain;
  6. 6Affomix Corporation, New Haven, Connecticut 06511, USA;
  7. 7Department of Computer Science, Yale University, New Haven, Connecticut 06520, USA;
  8. 8Program in Computational Biology and Bioinformatics, Yale University, New Haven, Connecticut 06520, USA
    1. 9 These authors contributed equally to this work.

    Abstract

    Complex biological processes are often regulated, at least in part, by the binding of transcription factors to their targets. Recently, considerable effort has been made to analyze the binding of relevant factors to the suite of targets they regulate, thereby generating a regulatory circuit map. However, for most studies the dynamics of binding have not been analyzed, and thus the temporal order of events and mechanisms by which this occurs are poorly understood. We globally analyzed in detail the temporal order of binding of several key factors involved in the salt response of yeast to their target genes. Analysis of Yap4 and Sko1 binding to their target genes revealed multiple temporal classes of binding patterns: (1) constant binding, (2) rapid induction, (3) slow induction, and (4) transient induction. These results demonstrate that individual transcription factors can have multiple binding patterns and help define the different types of temporal binding patterns used in eukaryotic gene regulation. To investigate these binding patterns further, we also analyzed the binding of seven other key transcription factors implicated in osmotic regulation, including Hot1, Msn1, Msn2, Msn4, Skn7, and Yap6, and found significant coassociation among the different factors at their gene targets. Moreover, the binding of several key factors was correlated with distinct classes of Yap4- and Sko1-binding patterns and with distinct types of genes. Gene expression studies revealed association of Yap4, Sko1, and other transcription factor-binding patterns with different gene expression patterns. The integration and analysis of binding and expression information reveals a complex dynamic and hierarchical circuit in which specific combinations of transcription factors target distinct sets of genes at discrete times to coordinate a rapid and important biological response.

    Keywords

    Footnotes

    | Table of Contents

    Life Science Alliance