PUBLICATION
The transcription factor Atonal homolog 8 regulates Gata4 and Friend of Gata-2 during vertebrate development
- Authors
- Rawnsley, D.R., Xiao, J., Lee, J.S., Liu, X., Mericko-Ishizuka, P., Kumar, V., He, J., Basu, A., Lu, M., Lynn, F.C., Pack, M., Gasa, R., Kahn, M.L.
- ID
- ZDB-PUB-170314-14
- Date
- 2013
- Source
- The Journal of biological chemistry 288: 24429-40 (Journal)
- Registered Authors
- He, Jie, Pack, Michael
- Keywords
- Cardiac Development, Development, Friend of Gata, Gata, Gene Knockout, Transcription Factors
- MeSH Terms
-
- Zebrafish/embryology*
- Zebrafish/genetics
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- Heart Ventricles/embryology
- Mice, Transgenic
- Myocardium/metabolism
- Organ Specificity/physiology
- Air Sacs/embryology
- GATA Transcription Factors/genetics
- GATA Transcription Factors/metabolism*
- Mice
- GATA4 Transcription Factor/genetics
- GATA4 Transcription Factor/metabolism*
- Organogenesis/physiology*
- DNA-Binding Proteins/genetics
- DNA-Binding Proteins/metabolism*
- Multiprotein Complexes/genetics
- Multiprotein Complexes/metabolism
- Transcription Factors/genetics
- Transcription Factors/metabolism*
- Basic Helix-Loop-Helix Transcription Factors/genetics
- Basic Helix-Loop-Helix Transcription Factors/metabolism*
- Animals
- Heart Atria/embryology
- PubMed
- 23836893 Full text @ J. Biol. Chem.
Citation
Rawnsley, D.R., Xiao, J., Lee, J.S., Liu, X., Mericko-Ishizuka, P., Kumar, V., He, J., Basu, A., Lu, M., Lynn, F.C., Pack, M., Gasa, R., Kahn, M.L. (2013) The transcription factor Atonal homolog 8 regulates Gata4 and Friend of Gata-2 during vertebrate development. The Journal of biological chemistry. 288:24429-40.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping