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| Subject Categories: Development |
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| The EMBO Journal
(2006) 25, 5201–5213, doi:10.1038/sj.emboj.7601379 Published online 19 October 2006 |
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| The Kruppel-like transcription factor KLF13 is a novel regulator of heart development |
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| Geneviève Lavallée1, 2, 3, Gregor Andelfinger1, 2, 3, Mathieu Nadeau1, 2, Chantal Lefebvre1, 2, Georges Nemer1, 2, 4, Marko E Horb1, 2 and Mona Nemer1, 2 |
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1 Institut de recherches cliniques de Montréal (IRCM), Montréal, Quebec, Canada 2 Université de Montréal, Montréal, Quebec, Canada To whom correspondence should be addressed Mona Nemer, 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 Marko E Horb, 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: marko.horb@ircm.qc.ca 3 These authors contributed equally to this work 4 Present address: Faculty of Medicine, American University of Beirut, Lebanon Received 7 April 2006; Accepted 6 September 2006; Published online 19 October 2006. |
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| Abstract |
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| 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. |
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| Keywords: ANP, BNP, cardiac transcription, GATA-4, Xenopus |
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Top of page MORE ARTICLES LIKE THISThese links to content published by NPG are automatically generated RESEARCHThe Kruppel-like transcription factor KLF13 is a novel regulator of heart development The EMBO Journal Article The cardiac transcription factors Nkx2-5 and GATA-4 are mutual cofactors The EMBO Journal Article (15 Sep 1997) GATA4 mutations cause human congenital heart defects and reveal an interaction with TBX5 Nature Letters to Editor (24 Jul 2003) |
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