The Transcription Factor Atonal homolog 8 Regulates Gata4 and Friend of Gata-2 during Vertebrate Development

• Published in: The Journal of biological chemistry Vol. 288; no. 34; pp. 24429 - 24440
• Main Authors: Rawnsley, David R., Xiao, Jiping, Lee, John S., Liu, Xi, Mericko-Ishizuka, Patricia, Kumar, Vinayak, He, Jie, Basu, Arindam, Lu, MinMin, Lynn, Francis C., Pack, Michael, Gasa, Rosa, Kahn, Mark L.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 23.08.2013; American Society for Biochemistry and Molecular Biology
• Subjects: Air Sacs - embryology; Animals; Basic Helix-Loop-Helix Transcription Factors - genetics; Basic Helix-Loop-Helix Transcription Factors - metabolism; Cardiac Development; Development; Developmental Biology; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Friend of Gata; Gata; GATA Transcription Factors - genetics; GATA Transcription Factors - metabolism; GATA4 Transcription Factor - genetics; GATA4 Transcription Factor - metabolism; Gene Knockout; Heart Atria - embryology; Heart Ventricles - embryology; Mice; Mice, Transgenic; Multiprotein Complexes - genetics; Multiprotein Complexes - metabolism; Myocardium - metabolism; Organ Specificity - physiology; Organogenesis - physiology; Transcription Factors; Transcription Factors - genetics; Transcription Factors - metabolism; Zebrafish - embryology; Zebrafish - genetics; Zebrafish Proteins - genetics; Zebrafish Proteins - metabolism; Development; Transcription Factors; Gene Knockout; Friend of Gata; Gata; Cardiac Development
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M113.463083

GATA and Friend of GATA (FOG) form a transcriptional complex that plays a key role in cardiovascular development in both fish and mammals. In the present study we demonstrate that the basic helix-loop-helix transcription factor Atonal homolog 8 (Atoh8) is required for development of the heart in fish but not in mice. Genetic studies reveal that Atoh8 interacts specifically with Gata4 and Fog1 during development of the heart and swim bladder in the fish. Biochemical studies reveal that ATOH8, GATA4, and FOG2 associate in a single complex in vitro. In contrast to fish, ATOH8-deficient mice exhibit normal cardiac development and loss of ATOH8 does not alter cardiac development in Gata4+/− mice. This species difference in the role of ATOH8 is explained in part by LacZ and GFP reporter alleles that reveal restriction of Atoh8 expression to atrial but not ventricular myocardium in the mouse. Our findings identify ATOH8 as a novel regulator of GATA-FOG function that is required for cardiac development in the fish but not the mouse. Whether ATOH8 modulates GATA-FOG function at other sites or in more subtle ways in mammals is not yet known. Background: GATA and FOG proteins are critical transcriptional regulators of multiple organ systems in vertebrate development. Results: The transcription factor Atoh8 genetically interacts with Gata4 and Fog1 in zebrafish development and mouse ATOH8 co-immunoprecipitates with FOG2. Conclusion: Atoh8 is a physical and genetic partner of Fog2 and GATA4. Significance: This study identifies Atoh8 as a transcriptional partner and regulator of the GATA-FOG transcriptional complex.