The Kruppel-like transcription factor KLF13 is a novel regulator of heart development

Authors

  • Geneviève Lavallée,

    1. Institut de recherches cliniques de Montréal (IRCM), Montréal, Quebec, Canada
    2. Université de Montréal, Montréal, Quebec, Canada
    Search for more papers by this author
    • These authors contributed equally to this work
  • Gregor Andelfinger,

    1. Institut de recherches cliniques de Montréal (IRCM), Montréal, Quebec, Canada
    2. Université de Montréal, Montréal, Quebec, Canada
    Search for more papers by this author
    • These authors contributed equally to this work
  • Mathieu Nadeau,

    1. Institut de recherches cliniques de Montréal (IRCM), Montréal, Quebec, Canada
    2. Université de Montréal, Montréal, Quebec, Canada
    Search for more papers by this author
  • Chantal Lefebvre,

    1. Institut de recherches cliniques de Montréal (IRCM), Montréal, Quebec, Canada
    2. Université de Montréal, Montréal, Quebec, Canada
    Search for more papers by this author
  • Georges Nemer,

    1. Institut de recherches cliniques de Montréal (IRCM), Montréal, Quebec, Canada
    2. Université de Montréal, Montréal, Quebec, Canada
    Search for more papers by this author
    • Present address: Faculty of Medicine, American University of Beirut, Lebanon
  • Marko E Horb,

    Corresponding author
    1. Institut de recherches cliniques de Montréal (IRCM), Montréal, Quebec, Canada
    2. Université de Montréal, Montréal, Quebec, Canada
    • Corresponding authors: Cardiac Growth and Differentiation Unit, Institut de recherches cliniques de Montréal (IRCM), 110, avenue des Pins Ouest, Montréal, Quebec, Canada H2W 1R7. Tel.: +1 514 987 5680; Fax: +1 514 987 5575; E-mail: mona.nemer@ircm.qc.ca or E-mail: marko.horb@ircm.qc.ca

    Search for more papers by this author
  • Mona Nemer

    Corresponding author
    1. Institut de recherches cliniques de Montréal (IRCM), Montréal, Quebec, Canada
    2. Université de Montréal, Montréal, Quebec, Canada
    • Corresponding authors: Cardiac Growth and Differentiation Unit, Institut de recherches cliniques de Montréal (IRCM), 110, avenue des Pins Ouest, Montréal, Quebec, Canada H2W 1R7. Tel.: +1 514 987 5680; Fax: +1 514 987 5575; E-mail: mona.nemer@ircm.qc.ca or E-mail: marko.horb@ircm.qc.ca

    Search for more papers by this author

Abstract

In humans, congenital heart defects occur in 1–2% of live birth, but the molecular mechanisms and causative genes remain unidentified in the majority of cases. We have uncovered a novel transcription pathway important for heart morphogenesis. We report that KLF13, a member of the Krüppel-like family of zinc-finger proteins, is expressed predominantly in the heart, binds evolutionarily conserved regulatory elements on cardiac promoters and activates cardiac transcription. KLF13 is conserved across species and knockdown of KLF13 in Xenopus embryos leads to atrial septal defects and hypotrabeculation similar to those observed in humans or mice with hypomorphic GATA-4 alleles. Physical and functional interaction with GATA-4, a dosage-sensitive cardiac regulator, provides a mechanistic explanation for KLF13 action in the heart. The data demonstrate that KLF13 is an important component of the transcription network required for heart development and suggest that KLF13 is a GATA-4 modifier; by analogy to other GATA-4 collaborators, mutations in KLF13 may be causative for congenital human heart disease.

Ancillary