Dynamics of cardiomyocyte transcriptome and chromatin landscape demarcates key events of heart development

Pawlak, Michał; Kedzierska, Katarzyna; Migdał, Maciej; Nahia, Karim Abu; Ramilowski, Jordan A.; Bugajski, Łukasz; Hashimoto, Kosuke; Marconi, Aleksandra; Piwocka, Katarzyna; Winata, Cecilia Lanny

doi:10.1101/gr.244491.118

Cited by 24 publications

(12 citation statements)

References 82 publications

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“…These studies revealed highly dynamic chromatin states accompanying cardiac differentiation and development. Specifically, ATAC-seq is widely used on precious in vivo cardiac samples to identify genomic regions that are enriched for TF binding and functional enhancer elements ( Jia et al, 2018 ; Yuan et al, 2018 ; Pawlak et al, 2019 ; Racioppi et al, 2019 ). Recently, accessible chromatin profiling has also enabled the discovery of enhancers specific to cardiac subpopulations, such as pacemaker cells ( Galang et al, 2020 ; van Eif et al, 2020 ) and endocardial populations ( Boogerd et al, 2017 ).…”

Section: Unmasking Heart Enhancers With Comparative and Functional Gementioning

confidence: 99%

“…Functional insights into cardiac enhancer regions continue to be made by studying TF occupancy and chromatin states upon the perturbation of cardiac TFs or signaling pathways in multiple organisms (e.g., Gata4, gata5 , Nkx2.5, Tbx5/tbx5, Tbx20, Hand2/hand2, Isl1, Foxf, Fgfr, Mek, and Ras ) ( He et al, 2014 ; Luna-Zurita et al, 2016 ; Boogerd et al, 2017 ; Jia et al, 2018 ; Pawlak et al, 2019 ; Racioppi et al, 2019 ), as well as in a human congenital heart disease (CHD) model (cardiomyocytes with a disease-associated missense mutation of GATA4 ) ( Ang et al, 2016 ). These studies reveal the master regulatory roles of cardiac TFs at the chromatin level.…”

Section: Unmasking Heart Enhancers With Comparative and Functional Gementioning

confidence: 99%

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Heart Enhancers: Development and Disease Control at a Distance

2021

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Bound by lineage-determining transcription factors and signaling effectors, enhancers play essential roles in controlling spatiotemporal gene expression profiles during development, homeostasis and disease. Recent synergistic advances in functional genomic technologies, combined with the developmental biology toolbox, have resulted in unprecedented genome-wide annotation of heart enhancers and their target genes. Starting with early studies of vertebrate heart enhancers and ending with state-of-the-art genome-wide enhancer discovery and testing, we will review how studying heart enhancers in metazoan species has helped inform our understanding of cardiac development and disease.

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Section: Unmasking Heart Enhancers With Comparative and Functional Gementioning

confidence: 99%

Section: Unmasking Heart Enhancers With Comparative and Functional Gementioning

confidence: 99%

Heart Enhancers: Development and Disease Control at a Distance

2021

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“…In several other studies, comparative analyses were performed between organisms other than zebrafish to detect evolutionarily conserved regions (ECRs) in the heart. The zebrafish system allows live enhancer assay, and conservation of enhancer function between zebrafish and mammals has been demonstrated [ 58 , 62 , 64 , 101 , 115 ]. Due to these features, many candidate enhancers identified in the mammalian system were validated in the zebrafish system [ 57 , 63 , 108 , 116 , 117 ].…”

Section: The Quest For Enhancers Involved In Heart Development and Functionmentioning

confidence: 99%

“…Recently, we capitalized on the power of genomics analyses and the zebrafish model system to capture the dynamics of regulatory landscape and gene regulatory network throughout the progression of zebrafish heart morphogenesis in vivo [ 58 ]. We combined transcriptome profiling (RNA-seq) with an assay for chromatin accessibility (ATAC-seq) on isolated CMs from wild-type zebrafish heart at key stages of heart morphogenesis corresponding to linear heart tube formation, chamber formation/differentiation, and heart maturation.…”

Section: The Quest For Enhancers Involved In Heart Development and Functionmentioning

confidence: 99%

“…The discovery of enhancers regulating multiple steps of heart development and regeneration has been greatly facilitated by the development of various approaches which allow their large-scale discovery. These include genome-wide profiling techniques such as chromatin immunoprecipitation followed by DNA sequencing (ChIP-seq) [ 20 , 55 , 56 , 57 , 58 ], computational predictions [ 59 , 60 ], and in vivo assay [ 61 , 62 , 63 , 64 ]. These approaches have been used on various model organisms such as the fruit fly Drosophila melanogaster [ 65 ], mouse Mus musculus [ 66 , 67 ], zebrafish Danio rerio [ 68 , 69 ], and the African clawed frog Xenopus laevis [ 70 , 71 ].…”

Section: Introductionmentioning

confidence: 99%

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Fish-Ing for Enhancers in the Heart

Parisi

Vashisht

Winata

2021

IJMS

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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.

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Hypoxia‐induced alterations of transcriptome and chromatin accessibility in HL‐1 cells

Wang

Duan

et al. 2020

IUBMB Life

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Cardiac hypoxia plays a significant role in various types of heart disease, and improper treatment of hypoxia often leads to myocardial cell damage or even death. Transcriptome profiling and open chromatin mapping have been used as powerful tools to understand the development of heart disease, but the interplay between gene expression and chromatin accessibility has not been extensively investigated in hypoxia-induced cardiac damage. In this study, with HL-1 cardiomyocytes as a model, we performed temporal profiling of transcriptome and chromatin accessibility to show the cardiac responses to hypoxia (for 4 and 8 hr) and reoxygenation (for 24 hr). With RNA-seq and ATAC-seq, we identified a total of 2,912 differentially expressed genes and 3,004 differential peaks across the whole genome and showed that these data were in good agreement with each other. For hypoxia-related genes, we also discovered high correlations between their ATAC-seq signals and mRNA levels, such as VEGF, Angpt1, Slc2a1, Bnip3, and Casp3 with Pearson correlations >0.7. Interestingly, after 24 hr reoxygenation, the expression levels of 235 genes were still significantly different from the counterparts in the control, suggesting that these genes need a longer recovery time after reoxygenation. In conclusion, our study shows the close relationship between alterations of transcriptome and chromatin accessibility after hypoxia exposure and reoxygenation, emphasizing the importance of open chromatin profiling in related studies. In addition, the profiled molecular responses here will be valuable resources for better understanding of the mechanisms responsible for hypoxia-induced heart disease in future.

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Dynamics of cardiomyocyte transcriptome and chromatin landscape demarcates key events of heart development

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Cited by 24 publications

References 82 publications

Heart Enhancers: Development and Disease Control at a Distance

Heart Enhancers: Development and Disease Control at a Distance

Fish-Ing for Enhancers in the Heart

Hypoxia‐induced alterations of transcriptome and chromatin accessibility in HL‐1 cells

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