Genome-wide fetalization of enhancer architecture in heart disease.
Cell Rep
; 40(12): 111400, 2022 09 20.
Article
em En
| MEDLINE
| ID: mdl-36130500
ABSTRACT
Heart disease is associated with re-expression of key transcription factors normally active only during prenatal development of the heart. However, the impact of this reactivation on the regulatory landscape in heart disease is unclear. Here, we use RNA-seq and ChIP-seq targeting a histone modification associated with active transcriptional enhancers to generate genome-wide enhancer maps from left ventricle tissue from up to 26 healthy controls, 18 individuals with idiopathic dilated cardiomyopathy (DCM), and five fetal hearts. Healthy individuals have a highly reproducible epigenomic landscape, consisting of more than 33,000 predicted heart enhancers. In contrast, we observe reproducible disease-associated changes in activity at 6,850 predicted heart enhancers. Combined analysis of adult and fetal samples reveals that the heart disease epigenome and transcriptome both acquire fetal-like characteristics, with 3,400 individual enhancers sharing fetal regulatory properties. We also provide a comprehensive data resource (http//heart.lbl.gov) for the mechanistic exploration of DCM etiology.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Cardiomiopatia Dilatada
/
Elementos Facilitadores Genéticos
Tipo de estudo:
Prognostic_studies
Limite:
Adult
/
Humans
Idioma:
En
Revista:
Cell Rep
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Estados Unidos