Combinatorial Functions of Transcription Factors and Epigenetic Factors in Heart Development and Disease
Heart malformations are the most common type of birth defect, affecting more than 2 % of newborns and causing significant morbidity and mortality. In the past two decades, studies have revealed the function and importance of cardiac transcription factors during heart development and in congenital heart disease. Transcription factors generally form complexes with other transcription factors and/or with chromatin factors to perform specific functions. This review focuses on how chromatin factors modify cardiac transcription factors during cardiovascular development and disease.
KeywordsCardiac development Cardiac disease T-box genes Epigenetic factors SWI/SNF-type chromatin remodeling factors
42.1 Transcription Factors in Heart Development
42.2 Chromatin Factors and Cardiac Differentiation
42.3 Future Directions and Clinical Implications
We have analyzed the functions of Baf60c, a component of the SWI/SNF-type chromatin remodeling complex, in heart development in vivo and in vitro, but the mechanism by which Baf60c is regulated is still unknown. An important question is whether the functions of Brg1 or Baf60c are altered in each type of tissue. If their functions do not vary, they may be regulated in a partner-dependent manner. One approach to confirm this hypothesis is to use ChIP-sequencing to compare Baf60c and Brg1 target genes in different tissues. Another question that must be addressed is how Baf60c’s expression pattern and dosage are regulated and which molecule(s) participate in this regulation. We found a candidate transcription factor that directly regulates Baf60c expression, but this molecule alone could not explain the dynamic change in Baf60c’s expression pattern. Further analysis is required to determine the molecular mechanisms of Baf60c regulation.
- 20.Takeuchi JK, Lou X, Alexander JM, et al. Chromatin remodelling complex dosage modulates transcription factor function in heart development. Nat Commun. 2011;2:187–97.Google Scholar
Open Access This chapter is distributed under the terms of the Creative Commons Attribution-Noncommercial 2.5 License (http://creativecommons.org/licenses/by-nc/2.5/), which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited. The images or other third party material in this chapter are included in the work's Creative Commons license, unless indicated otherwise in the credit line; if such material is not included in the work's Creative Commons license and the respective action is not permitted by statutory regulation, users will need to obtain permission from the license holder to duplicate, adapt or reproduce the material.