ArticleBMC developmental biology2008
GATA4/FOG2 transcriptional complex regulates Lhx9 gene expression in murine heart development.
Article in BMC developmental biology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 29 citations in OpenAlex.
- Global Evaluation of Congenital Heart Disease-Associated Non-Coding Variants.Research square · 2026Article
- Alternative LIM homeodomain splice variants are dynamically regulated at key developmental steps in vertebrates.Developmental dynamics : an official publication of the American Association of Anatomists · 2022Article
- Towards Understanding the Gene-Specific Roles of GATA Factors in Heart Development: Does GATA4 Lead the Way?International journal of molecular sciences · 2022Review
- LOX family and ZFPM2 as novel diagnostic biomarkers for malignant pleural mesothelioma.Biomarker research · 2020Article
- Exome-Wide Rare Variant Analyses in Sudden Infant Death Syndrome.The Journal of pediatrics · 2018Article
- Newborn blood DNA epigenetic variations and signaling pathway genes associated with Tetralogy of Fallot (TOF).PloS one · 2018Article
- Polycomb group RING finger proteins 3/5 activate transcription via an interaction with the pluripotency factor Tex10 in embryonic stem cells.The Journal of biological chemistry · 2017Article
- The Lhx9-integrin pathway is essential for positioning of the proepicardial organ.Development (Cambridge, England) · 2016Article
- The Lhx9 homeobox gene controls pineal gland development and prevents postnatal hydrocephalus.Brain structure & function · 2015Article
- Tcf21 regulates the specification and maturation of proepicardial cells.Development (Cambridge, England) · 2013Article
- Gata4 is required for formation of the genital ridge in mice.PLoS genetics · 2013Article
- The mammalian ovary from genesis to revelation.Endocrine reviews · 2009Review
- Coronary vessel development and insight towards neovascular therapy.International journal of experimental pathology · 2009Review
- Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
backgroundGATA4 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.
resultsHere we report identification of the Lhx9 gene as a direct target of the GATA4/FOG2 complex. We demonstrate that the developing mouse heart normally expresses truncated isoforms of Lhx9 - Lhx9alpha and Lhx9beta, and not the Lhx9-HD isoform that encodes a protein with an intact homeodomain. At E9.5 Lhx9alpha/beta expression is prominent in the epicardial primordium, septum transversum while Lhx9-HD is absent from this tissue; in the E11.5 heart LHX9alpha/beta-positive cells are restricted to the epicardial mesothelium. Thereafter in the control hearts Lhx9alpha/beta epicardial expression is promptly down-regulated; in contrast, mouse mutants with Fog2 gene loss fail to repress Lhx9alpha/beta expression. Chromatin immunoprecipitation from the E11.5 hearts demonstrated that Lhx9 is a direct target for GATA4 and FOG2. In transient transfection studies the expression driven by the cis-regulatory regions of Lhx9 was repressed by FOG2 in the presence of intact GATA4, but not the GATA4ki mutant that is impaired in its ability to bind FOG2.
conclusionIn summary, the Lhx9 gene represents the first direct target of the GATA4/FOG2 repressor complex in cardiac development.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.