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Genome organization in cardiomyocytes expressing mutated A-type lamins

Cardiomyopathy is a myocardial disorder, in which the heart muscle is structurally and functionally abnormal, often leading to heart failure. Dilated cardiomyopathy is characterized by a compromised left ventricular function and contributes significantly to the heart failure epidemic, which represen...

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Autores principales: Kervella, Marie, Jahier, Maureen, Meli, Albano C., Muchir, Antoine
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9585167/
https://www.ncbi.nlm.nih.gov/pubmed/36274847
http://dx.doi.org/10.3389/fcell.2022.1030950
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author Kervella, Marie
Jahier, Maureen
Meli, Albano C.
Muchir, Antoine
author_facet Kervella, Marie
Jahier, Maureen
Meli, Albano C.
Muchir, Antoine
author_sort Kervella, Marie
collection PubMed
description Cardiomyopathy is a myocardial disorder, in which the heart muscle is structurally and functionally abnormal, often leading to heart failure. Dilated cardiomyopathy is characterized by a compromised left ventricular function and contributes significantly to the heart failure epidemic, which represents a staggering clinical and public health problem worldwide. Gene mutations have been identified in 35% of patients with dilated cardiomyopathy. Pathogenic variants in LMNA, encoding nuclear A-type lamins, are one of the major causative causes of dilated cardiomyopathy (i.e. CardioLaminopathy). A-type lamins are type V intermediate filament proteins, which are the main components of the nuclear lamina. The nuclear lamina is connected to the cytoskeleton on one side, and to the chromatin on the other side. Among the models proposed to explain how CardioLaminopathy arises, the “chromatin model” posits an effect of mutated A-type lamins on the 3D genome organization and thus on the transcription activity of tissue-specific genes. Chromatin contacts with the nuclear lamina via specific genomic regions called lamina-associated domains lamina-associated domains. These LADs play a role in the chromatin organization and gene expression regulation. This review focuses on the identification of LADs and chromatin remodeling in cardiac muscle cells expressing mutated A-type lamins and discusses the methods and relevance of these findings in disease.
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spelling pubmed-95851672022-10-22 Genome organization in cardiomyocytes expressing mutated A-type lamins Kervella, Marie Jahier, Maureen Meli, Albano C. Muchir, Antoine Front Cell Dev Biol Cell and Developmental Biology Cardiomyopathy is a myocardial disorder, in which the heart muscle is structurally and functionally abnormal, often leading to heart failure. Dilated cardiomyopathy is characterized by a compromised left ventricular function and contributes significantly to the heart failure epidemic, which represents a staggering clinical and public health problem worldwide. Gene mutations have been identified in 35% of patients with dilated cardiomyopathy. Pathogenic variants in LMNA, encoding nuclear A-type lamins, are one of the major causative causes of dilated cardiomyopathy (i.e. CardioLaminopathy). A-type lamins are type V intermediate filament proteins, which are the main components of the nuclear lamina. The nuclear lamina is connected to the cytoskeleton on one side, and to the chromatin on the other side. Among the models proposed to explain how CardioLaminopathy arises, the “chromatin model” posits an effect of mutated A-type lamins on the 3D genome organization and thus on the transcription activity of tissue-specific genes. Chromatin contacts with the nuclear lamina via specific genomic regions called lamina-associated domains lamina-associated domains. These LADs play a role in the chromatin organization and gene expression regulation. This review focuses on the identification of LADs and chromatin remodeling in cardiac muscle cells expressing mutated A-type lamins and discusses the methods and relevance of these findings in disease. Frontiers Media S.A. 2022-10-07 /pmc/articles/PMC9585167/ /pubmed/36274847 http://dx.doi.org/10.3389/fcell.2022.1030950 Text en Copyright © 2022 Kervella, Jahier, Meli and Muchir. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cell and Developmental Biology
Kervella, Marie
Jahier, Maureen
Meli, Albano C.
Muchir, Antoine
Genome organization in cardiomyocytes expressing mutated A-type lamins
title Genome organization in cardiomyocytes expressing mutated A-type lamins
title_full Genome organization in cardiomyocytes expressing mutated A-type lamins
title_fullStr Genome organization in cardiomyocytes expressing mutated A-type lamins
title_full_unstemmed Genome organization in cardiomyocytes expressing mutated A-type lamins
title_short Genome organization in cardiomyocytes expressing mutated A-type lamins
title_sort genome organization in cardiomyocytes expressing mutated a-type lamins
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9585167/
https://www.ncbi.nlm.nih.gov/pubmed/36274847
http://dx.doi.org/10.3389/fcell.2022.1030950
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