GATA4/FOG2 transcriptional complex regulates <it>Lhx9 </it>gene expression in murine heart development

• Main Authors: Manuylov Nikolay L, Smagulova Fatima O, Leach Lyndsay L, Tevosian Sergei G
• Format: Article
• Language: English
• Published: BMC 2008-06-01
• Series: BMC Developmental Biology
• Online Access: http://www.biomedcentral.com/1471-213X/8/67

<p>Abstract</p> <p>Background</p> <p>GATA4 and FOG2 proteins are required for normal cardiac development in mice. It has been proposed that GATA4/FOG2 transcription complex exercises its function through gene activation as well as repression; however, targets of GATA4/FOG2 action in the heart remain elusive.</p> <p>Results</p> <p>Here we report identification of the <it>Lhx9 </it>gene as a direct target of the GATA4/FOG2 complex. We demonstrate that the developing mouse heart normally expresses truncated isoforms of <it>Lhx9 </it>– <it>Lhx9α </it>and <it>Lhx9β</it>, and not the <it>Lhx9-HD </it>isoform that encodes a protein with an intact homeodomain. At E9.5 <it>Lhx9α/β </it>expression is prominent in the epicardial primordium, septum transversum while <it>Lhx9-HD </it>is absent from this tissue; in the E11.5 heart LHX9α/β-positive cells are restricted to the epicardial mesothelium. Thereafter in the control hearts <it>Lhx9α/β </it>epicardial expression is promptly down-regulated; in contrast, mouse mutants with <it>Fog2 </it>gene loss fail to repress <it>Lhx9α/β </it>expression. Chromatin immunoprecipitation from the E11.5 hearts demonstrated that <it>Lhx9 </it>is a direct target for GATA4 and FOG2. In transient transfection studies the expression driven by the cis-regulatory regions of <it>Lhx9 </it>was repressed by FOG2 in the presence of intact GATA4, but not the GATA4^kimutant that is impaired in its ability to bind FOG2.</p> <p>Conclusion</p> <p>In summary, the <it>Lhx9 </it>gene represents the first direct target of the GATA4/FOG2 repressor complex in cardiac development.</p>