Genome-wide fetalization of enhancer architecture in heart disease
Autor: | Cailyn H. Spurrell, Iros Barozzi, Michael Kosicki, Brandon J. Mannion, Matthew J. Blow, Yoko Fukuda-Yuzawa, Neil Slaven, Sarah Y. Afzal, Jennifer A. Akiyama, Veena Afzal, Stella Tran, Ingrid Plajzer-Frick, Catherine S. Novak, Momoe Kato, Elizabeth A. Lee, Tyler H. Garvin, Quan T. Pham, Anne N. Kronshage, Steven Lisgo, James Bristow, Thomas P. Cappola, Michael P. Morley, Kenneth B. Margulies, Len A. Pennacchio, Diane E. Dickel, Axel Visel |
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Rok vydání: | 2022 |
Předmět: |
Cardiomyopathy
Dilated Adult Epigenomics Molecular biology [CP] Pediatric Research Initiative Enhancer Elements Cardiomyopathy 1.1 Normal biological development and functioning Medical Physiology heart disease Cardiovascular General Biochemistry Genetics and Molecular Biology Epigenome hIP-seq Rare Diseases Genetic Underpinning research Dilated genomics Genetics Humans transgenic assay fetalization Pediatric Human Genome Enhancer Elements Genetic enhancers regulatory elements Biochemistry and Cell Biology RNA-seq Transcription Factors |
Zdroj: | Cell reports, vol 40, iss 12 |
Popis: | 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. |
Databáze: | OpenAIRE |
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