@article {118,
	title = {Fish-Ing for Enhancers in the Heart.},
	journal = {Int J Mol Sci},
	volume = {22},
	year = {2021},
	month = {2021 Apr 10},
	abstract = {<p>Precise control of gene expression is crucial to ensure proper development and biological functioning of an organism. Enhancers are non-coding DNA elements which play an essential role in regulating gene expression. They contain specific sequence motifs serving as binding sites for transcription factors which interact with the basal transcription machinery at their target genes. Heart development is regulated by intricate gene regulatory network ensuring precise spatiotemporal gene expression program. Mutations affecting enhancers have been shown to result in devastating forms of congenital heart defect. Therefore, identifying enhancers implicated in heart biology and understanding their mechanism is key to improve diagnosis and therapeutic options. Despite their crucial role, enhancers are poorly studied, mainly due to a lack of reliable way to identify them and determine their function. Nevertheless, recent technological advances have allowed rapid progress in enhancer discovery. Model organisms such as the zebrafish have contributed significant insights into the genetics of heart development through enabling functional analyses of genes and their regulatory elements in vivo. Here, we summarize the current state of knowledge on heart enhancers gained through studies in model organisms, discuss various approaches to discover and study their function, and finally suggest methods that could further advance research in this field.</p>},
	keywords = {Animals, Binding Sites, Enhancer Elements, Genetic, Gene Expression Regulation, Developmental, Gene Regulatory Networks, Heart, Humans, Mutation, Transcription Factors, Zebrafish},
	issn = {1422-0067},
	doi = {10.3390/ijms22083914},
	author = {Parisi, Costantino and Vashisht, Shikha and Winata, Cecilia Lanny}
}
@article {112,
	title = {Dynamics of cardiomyocyte transcriptome and chromatin landscape demarcates key events of heart development.},
	journal = {Genome Res},
	volume = {29},
	year = {2019},
	month = {2019 03},
	pages = {506-519},
	abstract = {<p>Organogenesis involves dynamic regulation of gene transcription and complex multipathway interactions. Despite our knowledge of key factors regulating various steps of heart morphogenesis, considerable challenges in understanding its mechanism still exist because little is known about their downstream targets and interactive regulatory network. To better understand transcriptional regulatory mechanism driving heart development and the consequences of its disruption in vivo, we performed time-series analyses of the transcriptome and genome-wide chromatin accessibility in isolated cardiomyocytes (CMs) from wild-type zebrafish embryos at developmental stages corresponding to heart tube morphogenesis, looping, and maturation. We identified genetic regulatory modules driving crucial events of heart development that contained key cardiac TFs and are associated with open chromatin regions enriched for DNA sequence motifs belonging to the family of the corresponding TFs. Loss of function of cardiac TFs Gata5, Tbx5a, and Hand2 affected the cardiac regulatory networks and caused global changes in chromatin accessibility profile, indicating their role in heart development. Among regions with differential chromatin accessibility in mutants were highly conserved noncoding elements that represent putative enhancers driving heart development. The most prominent gene expression changes, which correlated with chromatin accessibility modifications within their proximal promoter regions, occurred between heart tube morphogenesis and looping, and were associated with metabolic shift and hematopoietic/cardiac fate switch during CM maturation. Our results revealed the dynamic regulatory landscape throughout heart development and identified interactive molecular networks driving key events of heart morphogenesis.</p>},
	keywords = {Animals, Cells, Cultured, Chromatin, Chromatin Assembly and Disassembly, Gene Expression Regulation, Developmental, Gene Regulatory Networks, Heart, Myocytes, Cardiac, Transcription Factors, Transcriptome, Zebrafish, Zebrafish Proteins},
	issn = {1549-5469},
	doi = {10.1101/gr.244491.118},
	author = {Pawlak, Michal and Kedzierska, Katarzyna Z and Migdal, Maciej and Nahia, Karim Abu and Ramilowski, Jordan A and Bugajski, Lukasz and Hashimoto, Kosuke and Marconi, Aleksandra and Piwocka, Katarzyna and Carninci, Piero and Winata, Cecilia L}
}
