Jumonji represses atrial natriuretic factor gene expression by inhibiting transcriptional activities of cardiac transcription factors

被引:67
作者
Kim, T
Chen, JQ
Sadoshima, J
Lee, Y
机构
[1] Univ Wisconsin, Sch Med, Dept Anat, Madison, WI 53706 USA
[2] Univ Med & Dent New Jersey, New Jersey Med Sch, Inst Cardiovasc Res, Newark, NJ 07103 USA
关键词
D O I
10.1128/MCB.24.23.10151-10160.2004
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:10151 / 10160
页数:10
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