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Induction of Id2 expression by cardiac transcription factors GATA4 and Nkx2.5
Author(s) -
Lim JoongYeon,
Kim Won Ho,
Kim Joon,
Park Sang Ick
Publication year - 2007
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.21396
Subject(s) - gata4 , transcription factor , electrophoretic mobility shift assay , biology , embryonic stem cell , gata transcription factor , promoter , microbiology and biotechnology , transcription (linguistics) , repressor , dna binding protein , cellular differentiation , cell fate determination , genetics , gene , gene expression , linguistics , philosophy
Inhibitor of differentiation/DNA binding (Id) proteins function as a regulator of helix‐loop‐helix proteins participating in cell lineage commitment and differentiation. Here, we observed a marked induction of Id2 during cardiomyocyte differentiation from P19CL6 murine embryonic teratocarcinoma stem cells, prompting us to investigate the upstream regulatory mechanism of Id2 induction. Computer analysis of Id2 promoter and subsequent electrophoretic mobility shift assay revealed several binding sites for GATA4 and Nkx2.5 within the Id2 promoter. By further deletion and mutation analysis of the respective binding site, we identified that two motifs located at −497/−502 and −264/−270 were functionally important for Id2 promoter activation by GATA4 and Nkx2.5, respectively. Overexpression of GATA4 and/or Nkx2.5 induced not only Id2 promoter activity but also Id2 protein expression. Additionally, Id proteins significantly inhibit the GATA4 and Nkx2.5‐dependent transcription, suggesting Id proteins may play a regulatory role in cardiogenesis. Collectively, our results demonstrate that GATA4 and Nkx2.5 could be one of the upstream regulators of Id2. J. Cell. Biochem. 103: 182–194, 2008. © 2007 Wiley‐Liss, Inc.