Jumonji represses atrial natriuretic factor gene expression by inhibiting transcriptional activities of cardiac transcription factors.
Mice with a homozygous knockout of the jumonji (jmj) gene showed abnormal heart development and defective regulation of cardiac-specific genes, including the atrial natriuretic factor (ANF). ANF is one of the earliest markers of cardiac differentiation and a hallmark for cardiac hypertrophy. Here, we show that JMJ represses ANF gene ... expression by inhibiting transcriptional activities of Nkx2.5 and GATA4. JMJ represses the Nkx2.5- or GATA4-dependent activation of the reporter genes containing the ANF promoter-enhancer or containing the Nkx2.5 or GATA4-binding consensus sequence. JMJ physically associates with Nkx2.5 and GATA4 in vitro and in vivo as determined by glutathione S-transferase pull-down and immunoprecipitation assays. Using mutational analyses, we mapped the protein-protein interaction domains in JMJ, Nkx2.5, and GATA4. We identified two DNA-binding sites of JMJ in the ANF enhancer by gel mobility shift assays. However, these JMJ-binding sites do not seem to mediate ANF repression by JMJ. Mutational analysis of JMJ indicates that the protein-protein interaction domain of JMJ mediates the repression of ANF gene expression. Therefore, JMJ may play important roles in the down-regulation of ANF gene expression and in heart development.
Mesh Terms:
Amino Acid Motifs, Animals, Atrial Natriuretic Factor, Binding Sites, Cell Differentiation, Cells, Cultured, DNA, DNA Mutational Analysis, DNA Primers, Enhancer Elements, Genetic, Fibroblasts, Gene Expression Regulation, Developmental, Genes, Reporter, Glutathione Transferase, Homeodomain Proteins, Homozygote, Immunoprecipitation, Mice, Mice, Knockout, Mutation, Myocardium, Myocytes, Cardiac, Nerve Tissue Proteins, Plasmids, Polycomb Repressive Complex 2, Promoter Regions, Genetic, Protein Binding, Protein Biosynthesis, Protein Structure, Tertiary, Rats, Transcription Factors, Transcription, Genetic, Transcriptional Activation, Transfection
Amino Acid Motifs, Animals, Atrial Natriuretic Factor, Binding Sites, Cell Differentiation, Cells, Cultured, DNA, DNA Mutational Analysis, DNA Primers, Enhancer Elements, Genetic, Fibroblasts, Gene Expression Regulation, Developmental, Genes, Reporter, Glutathione Transferase, Homeodomain Proteins, Homozygote, Immunoprecipitation, Mice, Mice, Knockout, Mutation, Myocardium, Myocytes, Cardiac, Nerve Tissue Proteins, Plasmids, Polycomb Repressive Complex 2, Promoter Regions, Genetic, Protein Binding, Protein Biosynthesis, Protein Structure, Tertiary, Rats, Transcription Factors, Transcription, Genetic, Transcriptional Activation, Transfection
Mol. Cell. Biol.
Date: Dec. 01, 2004
PubMed ID: 15542826
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