The heart performs a vital function in circulating oxygen-carrying blood and nutrients throughout the body. Specialized cell types constitute essential components of the heart to ensure its life-sustaining activity. The core genetic program underlying heart development is largely conserved across metazoans and aberrations to this process could result in congenital heart disease. Despite our knowledge of key factors regulating various steps of heart morphogenesis, little is known about their downstream gene regulatory network. To better understand the dynamics of gene regulatory landscape and how it translates into the diversity of cardiac cell identity, we utilized several zebrafish transgenic lines expressing EGFP in the cardiomyocytes and cells of the cardiac pacemakers and profiled the transcriptome and chromatin states in these specialized cell types. Our analyses revealed major gene expression changes and chromatin rearrangement throughout different stages of heart morphogenesis and identified genetic regulatory hubs driving key events of heart development. Furthermore, loss of function of cardiac transcription factors Gata5, Tbx5a, and Hand2 affected these regulatory networks and caused global changes in chromatin accessibility profile. Among genomic regions with dynamic chromatin accessibility were highly conserved non-coding regulatory elements that represent putative enhancers implicated in heart development. To elucidate the role of these enhancers in heart development and disease, we combine both experimental and computational approaches for discovery and biological validation in the zebrafish model system. Ultimately, we seek to characterize the contribution of the dynamic transcriptional regulatory landscape to heart development and identify novel elements (both genic and non-genic) that are associated with congenital heart disease.

 

Dr. Cecilia Winata obtained her Bachelor’s degree in Biology at the National University of Singapore. In 2009, she obtained her PhD in 2009 from the National University of Singapore under the supervision of Profs. Gong Zhiyuan and Vladimir Korzh. She then joined the Genome Institute of Singapore as a postdoctoral fellow in the lab of Dr. Sinnakaruppan Mathavan, where she picked up genomics and applied them to study gene regulation in maternal to zygotic transition and functional characterization of the Zic3 transcription factor. In 2014, she became a Max Planck/IIMCB group leader at the International Institute of Molecular and Cell Biology in Warsaw, Poland. Her lab studies transcriptional regulation and epigenetics during heart development, as well as post-transcriptional regulation of maternal mRNAs in early embryonic development in zebrafish.