Epigenetic State Changes Underlie Metabolic Switch in Mouse Post-Infarction Border Zone Cardiomyocytes

Myocardial infarction causes ventricular muscle loss and formation of scar tissue. The surviving myocardium in the border zone, located adjacent to the infarct, undergoes profound changes in function, structure and composition. How and to what extent these changes of border zone cardiomyocytes are r...

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Autores principales:	Marie Günthel, Karel van Duijvenboden, Dennis E. M. de Bakker, Ingeborg B. Hooijkaas, Jeroen Bakkers, Phil Barnett, Vincent M. Christoffels
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	transcriptome myocardial infarction border zone epigenetics H3K27ac nuclear RNA-sequencing Diseases of the circulatory (Cardiovascular) system RC666-701
Acceso en línea:	https://doaj.org/article/e52b4995265f4ae59569e0a64eefa134
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spelling	oai:doaj.org-article:e52b4995265f4ae59569e0a64eefa1342021-11-25T18:00:11ZEpigenetic State Changes Underlie Metabolic Switch in Mouse Post-Infarction Border Zone Cardiomyocytes10.3390/jcdd81101342308-3425https://doaj.org/article/e52b4995265f4ae59569e0a64eefa1342021-10-01T00:00:00Zhttps://www.mdpi.com/2308-3425/8/11/134https://doaj.org/toc/2308-3425Myocardial infarction causes ventricular muscle loss and formation of scar tissue. The surviving myocardium in the border zone, located adjacent to the infarct, undergoes profound changes in function, structure and composition. How and to what extent these changes of border zone cardiomyocytes are regulated epigenetically is not fully understood. Here, we obtained transcriptomes of PCM-1-sorted mouse cardiomyocyte nuclei of healthy left ventricle and 7 days post myocardial infarction border zone tissue. We validated previously observed downregulation of genes involved in fatty acid metabolism, oxidative phosphorylation and mitochondrial function in border zone-derived cardiomyocytes, and observed a modest induction of genes involved in glycolysis, including <i>Slc2a1</i> (Glut1) and <i>Pfkp</i>. To gain insight into the underlying epigenetic regulatory mechanisms, we performed H3K27ac profiling of healthy and border zone cardiomyocyte nuclei. We confirmed the switch from Mef2- to AP-1 chromatin association in border zone cardiomyocytes, and observed, in addition, an enrichment of PPAR/RXR binding motifs in the sites with reduced H3K27ac signal. We detected downregulation and accompanying epigenetic state changes at several key PPAR target genes including <i>Ppargc1a</i> (PGC-1α), <i>Cpt2</i>, <i>Ech1</i>, <i>Fabpc3</i> and <i>Vldrl</i> in border zone cardiomyocytes. These data indicate that changes in epigenetic state and gene regulation underlie the maintained metabolic switch in border zone cardiomyocytes.Marie GünthelKarel van DuijvenbodenDennis E. M. de BakkerIngeborg B. HooijkaasJeroen BakkersPhil BarnettVincent M. ChristoffelsMDPI AGarticletranscriptomemyocardial infarctionborder zoneepigeneticsH3K27acnuclear RNA-sequencingDiseases of the circulatory (Cardiovascular) systemRC666-701ENJournal of Cardiovascular Development and Disease, Vol 8, Iss 134, p 134 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	transcriptome myocardial infarction border zone epigenetics H3K27ac nuclear RNA-sequencing Diseases of the circulatory (Cardiovascular) system RC666-701
spellingShingle	transcriptome myocardial infarction border zone epigenetics H3K27ac nuclear RNA-sequencing Diseases of the circulatory (Cardiovascular) system RC666-701 Marie Günthel Karel van Duijvenboden Dennis E. M. de Bakker Ingeborg B. Hooijkaas Jeroen Bakkers Phil Barnett Vincent M. Christoffels Epigenetic State Changes Underlie Metabolic Switch in Mouse Post-Infarction Border Zone Cardiomyocytes
description	Myocardial infarction causes ventricular muscle loss and formation of scar tissue. The surviving myocardium in the border zone, located adjacent to the infarct, undergoes profound changes in function, structure and composition. How and to what extent these changes of border zone cardiomyocytes are regulated epigenetically is not fully understood. Here, we obtained transcriptomes of PCM-1-sorted mouse cardiomyocyte nuclei of healthy left ventricle and 7 days post myocardial infarction border zone tissue. We validated previously observed downregulation of genes involved in fatty acid metabolism, oxidative phosphorylation and mitochondrial function in border zone-derived cardiomyocytes, and observed a modest induction of genes involved in glycolysis, including <i>Slc2a1</i> (Glut1) and <i>Pfkp</i>. To gain insight into the underlying epigenetic regulatory mechanisms, we performed H3K27ac profiling of healthy and border zone cardiomyocyte nuclei. We confirmed the switch from Mef2- to AP-1 chromatin association in border zone cardiomyocytes, and observed, in addition, an enrichment of PPAR/RXR binding motifs in the sites with reduced H3K27ac signal. We detected downregulation and accompanying epigenetic state changes at several key PPAR target genes including <i>Ppargc1a</i> (PGC-1α), <i>Cpt2</i>, <i>Ech1</i>, <i>Fabpc3</i> and <i>Vldrl</i> in border zone cardiomyocytes. These data indicate that changes in epigenetic state and gene regulation underlie the maintained metabolic switch in border zone cardiomyocytes.
format	article
author	Marie Günthel Karel van Duijvenboden Dennis E. M. de Bakker Ingeborg B. Hooijkaas Jeroen Bakkers Phil Barnett Vincent M. Christoffels
author_facet	Marie Günthel Karel van Duijvenboden Dennis E. M. de Bakker Ingeborg B. Hooijkaas Jeroen Bakkers Phil Barnett Vincent M. Christoffels
author_sort	Marie Günthel
title	Epigenetic State Changes Underlie Metabolic Switch in Mouse Post-Infarction Border Zone Cardiomyocytes
title_short	Epigenetic State Changes Underlie Metabolic Switch in Mouse Post-Infarction Border Zone Cardiomyocytes
title_full	Epigenetic State Changes Underlie Metabolic Switch in Mouse Post-Infarction Border Zone Cardiomyocytes
title_fullStr	Epigenetic State Changes Underlie Metabolic Switch in Mouse Post-Infarction Border Zone Cardiomyocytes
title_full_unstemmed	Epigenetic State Changes Underlie Metabolic Switch in Mouse Post-Infarction Border Zone Cardiomyocytes
title_sort	epigenetic state changes underlie metabolic switch in mouse post-infarction border zone cardiomyocytes
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/e52b4995265f4ae59569e0a64eefa134
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Epigenetic State Changes Underlie Metabolic Switch in Mouse Post-Infarction Border Zone Cardiomyocytes

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