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

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

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Titre: The Kruppel-like transcription factor KLF13 is a novel regulator of heart development
Auteur: Nemer, Georges; Horb, Marko E.; Nemer, Mona; Nadeau, Mathieu; Lefebvre, Chantal; Lavallée, Geneviève; Andelfinger, Gregor
Résumé: In human, 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 lead to atrial septal defects and hypotrabeculation similar to those observed in human 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.
Date: 2006
URI: http://hdl.handle.net/10393/12786

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