High impact information on GATA4

• BMPs apparently function, in part, by affecting the levels of the GATA4 transcription factor, and work in parallel to FGF signaling from the cardiac mesoderm [1].
• By systematic mutagenesis and gel shift analysis of this enhancer, we demonstrate that GATA4/5/6, YY1 and SMAD1/4 are all necessary for BMP-mediated induction and heart-specific expression of CAR3 [2].
• SMAD-mediated modulation of YY1 activity regulates the BMP response and cardiac-specific expression of a GATA4/5/6-dependent chick Nkx2.5 enhancer [2].
• Moreover, Y27632 induced precocious expression of cardiac alpha-actin, an early marker of cardiomyocyte differentiation, coincident with the upregulated expression of serum response factor and GATA4 [3].
• BMP-2 was able to induce Nkx2-5 expression ectopically within the anterior head domain, while GATA-4 was also induced more caudally [4].

Biological context of GATA4

• GATA-4 regulates cardiac morphogenesis through transactivation of the N-cadherin gene [5].
• We therefore concluded that the cardia bifida observed in the GATA-4-deleted model is caused by the transcriptional down-regulation of N-cadherin expression [5].
• RT-PCR using mRNAs extracted from cardiac tubes revealed that the GATA-4-specific siRNA selectively suppresses expression of N-cadherin mRNA, one of the genes essential for the single heart formation, without affecting other cardiac marker mRNAs [5].
• Analysis of the N-cadherin gene promoter activity using a luciferase reporter gene system and electrophoretic mobility shift assays revealed that GATA-4 binds directly to the N-cadherin gene promoter region, thereby transactivating its expression [5].
• The Gata4 mRNA was expressed in both sexes, and sex differences were not revealed throughout the observational period [6].

Anatomical context of GATA4

• Cardia bifida is known to occur in animal models lacking the cardiogenic transcriptional factor GATA-4 [5].
• Treatment with small interfering RNAs (siRNA) specifically targeting GATA-4 into cardiac mesodermal cells led to the development of cardia bifida in chick embryos [5].
• In addition, ES + CM co-culture activated crucial transcription factors (sox 17alpha, HNF3beta, and GATA 4) required for hepatocyte development by day 1. mRNA for albumin and especially a-fetoprotein were also increased by culture days 2 and 4 [7].

References