We are striving to understand the mechanism by which the thousands of genes in our genomes are switched on or off during lineage commitment and differentiation. We study the regulation of cardiac transcription at multiple levels, including DNA-binding transcription factors, chromatin states, and 3D genomic interactions. We have a long-term interest in the function of DNA-binding transcription factors, especially those that are involved in human congenital heart defects, which happen to be some of the most critical for cardiac differentiation and development. Using a balance of in vivo models and in vitro directed differentiation systems, we are unraveling the transcription factor networks that regulate broad sets of genes critical for several aspects of heart development. We are also keenly interested in chromatin-level regulation of gene expression. This includes chromatin remodeling complexes: their composition, function, and targeting to genomic loci. The lab also investigates histone modifications and how they are deployed to facilitate broad gene expression programs. Since genes encoding histone modifying proteins are mutated in some congenital heart defects, we are keen to understand how these mutations affect specific regulatory networks. Finally, we are defining the function of enhancer elements in gene regulation, and how specific enhancers are regulated to modulate target gene expression, including 3D genomic interactions.
- Luna-Zurita L., Stirnimann C.U., Glatt S., Kaynak B.L., Thomas S., Baudin F., Samee Md.A.H., He D., Small E.M., Mileikovsky M., Nagy A., Holloway A.K., Pollard K.S., Muller C.W., & Bruneau B.G. (2016) Complex interdependence regulates heterotypic transcription factor distribution and coordinates cardiogenesis. Cell 164:999-1014
- Ang S.-Y., Uebersohn A., Spencer C.I., Huang Y., Lee J.-E., Ge K., & Bruneau B.G. (2016) KMT2D regulates specific programs in heart development via histone H3 lysine 4 dimethylation. Development 143:810-821
- Wamstad J.A., Alexander J.M., Truty R.M., Shrikumar A., Li F., Eilertson K.E., Ding H., Wylie J.N., Pico A.R., Capra J.A., Erwin G., Kattman S.J., Keller G.M., Srivastava D., Levine S.S., Pollard K.S., Holloway A.K., Boyer L.A.*, & Bruneau B.G.* (2012) Dynamic and coordinated epigenetic regulation of developmental transitions in the cardiac lineage. Cell 151:206-220 (* Corresponding authors)
- Delgado-Olguín P., Huang Y., Li X., Christodoulou D., Seidman C.E., Seidman J.G., Tarakhovsky A., & Bruneau B.G. (2012) Epigenetic repression of cardiac progenitor gene expression by Ezh2 is required for postnatal cardiac homeostasis. Nature Genetics 44(3):343-7