Eric Svensson
Research Summary / Selected Publications
My general research interest is to further our understanding of the transcriptional regulation of cardiac development with the expectation that this will lead to an improved understanding of the molecular basis of congenital heart disease. Further, elucidation of the transcriptional regulation of heart formation may also suggest potential strategies to repair a heart damaged by a myocardial infarction and lead to novel insights into the origins of cardiac stem cells.
Significant progress has been made in the last decade in elucidating the molecular mechanisms regulating cardiac morphogenesis, but this process is still only partially understood. To date, only a limited number of genes have been identified that play a role in the transcriptional regulation of heart development. Mutations in several of these genes have now been shown to cause human congenital heart disease. We have previously identified a gene critical for normal heart development called FOG-2, a member of the FOG family of transcriptional modulators that also includes FOG-1 and U-shaped. FOG-2 functions as a transcriptional co-repressor by physically associating with GATA4, a cardiac-enriched transcriptional activator. We have found that mice with a targeted disruption of the FOG-2 gene die in mid-gestation from cardiac failure secondary to cardiac malformations. We have also found that FOG genes are required for zebrafish cardiac development, suggesting that the transcriptional pathways regulating cardiac development are conserved across vertebrates. Taken together, these results demonstrate the importance of FOG-2 in cardiogenesis and suggest that transcriptional repression, in addition to activation, plays a critical role in cardiac development. Ongoing work in the lab is directed toward identifying the transcriptional pathways regulating FOG-2 expression and characterizing the molecular mechanism responsible for FOG-2's transcriptional repression.
My general research interest is to further our understanding of the transcriptional regulation of cardiac development with the expectation that this will lead to an improved understanding of the molecular basis of congenital heart disease. Further, elucidation of the transcriptional regulation of heart formation may also suggest potential strategies to repair a heart damaged by a myocardial infarction and lead to novel insights into the origins of cardiac stem cells.
Significant progress has been made in the last decade in elucidating the molecular mechanisms regulating cardiac morphogenesis, but this process is still only partially understood. To date, only a limited number of genes have been identified that play a role in the transcriptional regulation of heart development. Mutations in several of these genes have now been shown to cause human congenital heart disease. We have previously identified a gene critical for normal heart development called FOG-2, a member of the FOG family of transcriptional modulators that also includes FOG-1 and U-shaped. FOG-2 functions as a transcriptional co-repressor by physically associating with GATA4, a cardiac-enriched transcriptional activator. We have found that mice with a targeted disruption of the FOG-2 gene die in mid-gestation from cardiac failure secondary to cardiac...
Kim, G.K., Samant, S. A., Earley, J. U., and Svensson, E. C. (2009) “Translational Control of FOG-2 Expression in Cardiomyocytes by MicroRNA-130A”, PLOS One, 4, e6161. PubMed Link
Roche, A. E., Bassett, B. J., Samant, S. A., Hong, W., Blobel, G. A., and Svensson, E. C. (2008) “The Zinc Finger and C-terminal Domains of MTA proteins are required for FOG-2-mediated Transcriptional Repression via the NuRD Complex", Journal of Molecular and Cellular Cardiology 44, 352-360. PubMed Link
Dale, R. M., Remo, B. F., and Svensson, E. C. (2007) “An Alternative Transcript of the FOG-2 Gene Encodes a FOG-2 Isoform lacking the FOG Repression Motif” Biochem. Biophys. Res. Commun., 357, 683-687. PubMed Link
Flagg, A. E., Early, J. U., and Svensson, E. C. (2007) "FOG-2 Attenuates Endothelial-to Mesenchymal Transformation in the Endocardial Cushions of the Developing Heart" Dev. Biol., 304, 308-316. PubMed Link
Walton, R.Z., Bruce, A., Olivey, H. E., Najib, K., Johnson, V., Early, J., Ho, R.K. and Svensson, E.C. (2006) "Fog1 is Required for Cardiac Looping in Zebrafish" Dev. Biol., 289, 482-493. PubMed Link
Svensson, E. C., Wilk, J., Dale, R. M., and Modrell, M. (2005) "The role of the transcriptional co-repressor FOG-2 in cardiac development" in Cardiovascular Development and Congenital Malformations Artman, M., Benson, D.W., Srivastava, D., and Nakazawa, M. (eds), p125-127.
Lin, A. C., Roche, A. E., Wilk, J. and Svensson, E. C. (2004). "The N Termini of Friend of GATA (FOG) Proteins Define a Novel Transcriptional Repression Motif and a Superfamily of Transcriptional Repressors." J Biol Chem 279: 55017-23.
PubMed Link
Svensson, E. C., Huggins, G. S., Lin, H., Clendenin, C., Jiang, F., Tufts, R., Dardik, F. B. and Leiden, J. M. (2000). "A syndrome of tricuspid atresia in mice with a targeted mutation of the gene encoding Fog-2." Nat Genet 25: 353-6. PubMed Link
Svensson, E. C., Huggins, G. S., Dardik, F. B., Polk, C. E. and Leiden, J. M. (2000). "A functionally conserved N-terminal domain of the friend of GATA-2 (FOG-2) protein represses GATA4-dependent transcription." J Biol Chem 275: 20762-9. PubMed Link
Svensson, E. C., Tufts, R. L., Polk, C. E. and Leiden, J. M. (1999). "Molecular cloning of FOG-2: a modulator of transcription factor GATA-4 in cardiomyocytes." Proc Natl Acad Sci U S A 96: 956-61. PubMed Link
Kim, G.K., Samant, S. A., Earley, J. U., and Svensson, E. C. (2009) “Translational Control of FOG-2 Expression in Cardiomyocytes by MicroRNA-130A”, PLOS One, 4, e6161. PubMed Link
Roche, A. E., Bassett, B. J., Samant, S. A., Hong, W., Blobel, G. A., and Svensson, E. C. (2008) “The Zinc Finger and C-terminal Domains of MTA proteins are required for FOG-2-mediated Transcriptional Repression via the NuRD Complex", Journal of Molecular and Cellular Cardiology 44, 352-360. PubMed Link
Dale, R. M., Remo, B. F., and Svensson, E. C. (2007) “An Alternative Transcript of the FOG-2 Gene Encodes a FOG-2 Isoform lacking the FOG Repression Motif” Biochem. Biophys. Res. Commun., 357, 683-687. PubMed Link
Flagg, A. E., Early, J. U., and Svensson, E. C. (2007) "FOG-2 Attenuates Endothelial-to Mesenchymal Transformation in the Endocardial Cushions of the Developing Heart" Dev. Biol., 304, 308-316. PubMed Link
Walton, R.Z., Bruce, A., Olivey, H. E., Najib, K., Johnson, V., Early, J., Ho, R.K. and Svensson, E.C. (2006) "Fog1 is Required for Cardiac Looping in Zebrafish" Dev. Biol., 289, 482-493. PubMed Link
