Congenital heart disease (CHD) is the most common type of developmental defect, with high rates of morbidity in infants. The transcription factor GATA-binding factor 4 (GATA4) has been reported to serve a critical role in embryogenesis and cardiac development. Our previous study reported a heterozygous GATA4 c.1306C>T (p.H436Y) mutation in four Chinese infants with congenital heart defects. In the present study, functional analysis of the GATA4 H436Y mutation was performed in vitro. The functional effect of GATA4 mutation was compared with GATA4 wild-type using a dual-luciferase reporter assay system and immunofluorescence. Electrophoretic mobility-shift assays were performed to explore the binding affinity of the mutated GATA4 to the heart and neural crest derivatives expressed 2 (HAND2) gene. The results revealed that the mutation had no effect on normal nuclear localization, but resulted in diminished GATA-binding affinity to HAND2 and significantly decreased gene transcriptional activation. These results indicated that this GATA4 mutation may not influence cellular localization in transfected cells, but may affect the affinity of the GATA-binding site on HAND2 and decrease transcriptional activity, thus suggesting that the GATA4 mutation may be associated with the pathogenesis of CHD.
[1]Univ Sci & Technol China, Affiliated Hosp 1, Div Life Sci & Med, 1 Tianehu Rd, Hefei 230036, Anhui, Peoples R China;
[2]Anhui Med Univ, Anhui Prov Hosp, Dept Paediat, Hefei 230001, Anhui, Peoples R China;
[3]Fudan Univ, Childrens Hosp, Cardiovasc Ctr, 399 Wanyuan Rd, Shanghai 201102, Peoples R China;
[4]Univ Sci & Technol China, Anhui Women & Child Hlth Care Hosp, Dept Neonatol, Hefei 230027, Anhui, Peoples R China;
[5]Univ Sci & Technol China, Dept Life Sci, Hefei 230027, Anhui, Peoples R China
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