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

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 downstre...

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Autores principales: Pawlak, Michal, Kedzierska, Katarzyna Z., Migdal, Maciej, Nahia, Karim Abu, Ramilowski, Jordan A., Bugajski, Lukasz, Hashimoto, Kosuke, Marconi, Aleksandra, Piwocka, Katarzyna, Carninci, Piero, Winata, Cecilia L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6396412/
https://www.ncbi.nlm.nih.gov/pubmed/30760547
http://dx.doi.org/10.1101/gr.244491.118
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author Pawlak, Michal
Kedzierska, Katarzyna Z.
Migdal, Maciej
Nahia, Karim Abu
Ramilowski, Jordan A.
Bugajski, Lukasz
Hashimoto, Kosuke
Marconi, Aleksandra
Piwocka, Katarzyna
Carninci, Piero
Winata, Cecilia L.
author_facet Pawlak, Michal
Kedzierska, Katarzyna Z.
Migdal, Maciej
Nahia, Karim Abu
Ramilowski, Jordan A.
Bugajski, Lukasz
Hashimoto, Kosuke
Marconi, Aleksandra
Piwocka, Katarzyna
Carninci, Piero
Winata, Cecilia L.
author_sort Pawlak, Michal
collection PubMed
description 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.
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spelling pubmed-63964122019-03-18 Dynamics of cardiomyocyte transcriptome and chromatin landscape demarcates key events of heart development Pawlak, Michal Kedzierska, Katarzyna Z. Migdal, Maciej Nahia, Karim Abu Ramilowski, Jordan A. Bugajski, Lukasz Hashimoto, Kosuke Marconi, Aleksandra Piwocka, Katarzyna Carninci, Piero Winata, Cecilia L. Genome Res Resource 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. Cold Spring Harbor Laboratory Press 2019-03 /pmc/articles/PMC6396412/ /pubmed/30760547 http://dx.doi.org/10.1101/gr.244491.118 Text en © 2019 Pawlak et al.; Published by Cold Spring Harbor Laboratory Press http://creativecommons.org/licenses/by-nc/4.0/ This article, published in Genome Research, is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
spellingShingle Resource
Pawlak, Michal
Kedzierska, Katarzyna Z.
Migdal, Maciej
Nahia, Karim Abu
Ramilowski, Jordan A.
Bugajski, Lukasz
Hashimoto, Kosuke
Marconi, Aleksandra
Piwocka, Katarzyna
Carninci, Piero
Winata, Cecilia L.
Dynamics of cardiomyocyte transcriptome and chromatin landscape demarcates key events of heart development
title Dynamics of cardiomyocyte transcriptome and chromatin landscape demarcates key events of heart development
title_full Dynamics of cardiomyocyte transcriptome and chromatin landscape demarcates key events of heart development
title_fullStr Dynamics of cardiomyocyte transcriptome and chromatin landscape demarcates key events of heart development
title_full_unstemmed Dynamics of cardiomyocyte transcriptome and chromatin landscape demarcates key events of heart development
title_short Dynamics of cardiomyocyte transcriptome and chromatin landscape demarcates key events of heart development
title_sort dynamics of cardiomyocyte transcriptome and chromatin landscape demarcates key events of heart development
topic Resource
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6396412/
https://www.ncbi.nlm.nih.gov/pubmed/30760547
http://dx.doi.org/10.1101/gr.244491.118
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