Jumonji Represses Atrial Natriuretic Factor Gene Expression by Inhibiting Transcriptional Activities of Cardiac Transcription Factors

• DOI: 10.1128/mcb.24.23.10151-10160.2004
• Publication Date: 2004-11-12T23:37:59Z
• Authors: Tae-gyun Kim; Junqin Chen; Junich Sadoshima; Youngsook Lee
• Keywords: GATA4

Mice with a homozygous knockout of the jumonji (jmj) gene showed abnormal heart development and defective regulation cardiac-specific genes, including atrial natriuretic factor (ANF). ANF is one earliest markers cardiac differentiation hallmark for hypertrophy. Here, we show that JMJ represses expression by inhibiting transcriptional activities Nkx2.5 GATA4. Nkx2.5- or GATA4-dependent activation reporter genes containing promoter-enhancer GATA4-binding consensus sequence. physically associates GATA4 in vitro vivo as determined glutathione S-transferase pull-down immunoprecipitation assays. Using mutational analyses, mapped protein-protein interaction domains JMJ, Nkx2.5, We identified two DNA-binding sites enhancer gel mobility shift However, these JMJ-binding do not seem to mediate repression JMJ. Mutational analysis indicates domain mediates expression. Therefore, may play important roles down-regulation development.