A gene regulatory element modulates myosin expression and controls cardiomyocyte response to stress
Anglen, T.; Kaplow, I. M.; Choi, B.; Dewars, E.; Perelli, R. M.; Hagy, K. T.; Tran, D.; Ramaker, M. E.; Shah, S.; Jung, I.; Landstrom, A. P.; Karra, R.; Diao, Y.; Gersbach, C. A.
Show abstract
A hallmark of heart disease is gene dysregulation and reactivation of fetal gene programs. Reactivation of these fetal programs has compensatory effects during heart failure, depending on the type and stage of the underlying cardiomyopathy. Thousands of putative cardiac gene regulatory elements have been identified that may control these programs, but their functions are largely unknown. We profile genome-wide changes to gene expression and chromatin structure in cardiomyocytes derived from human pluripotent stem cells. We identify and characterize a gene regulatory element essential for the regulation of MYH6, which encodes human fetal myosin. Using chromatin conformation assays in combination with epigenome editing, we find that gene regulation is mediated by direct interaction between MYH6 and the enhancer. We also find that enhancer activation alters cardiomyocyte response to the hypertrophy-inducing peptide endothelin-1. Enhancer activation prevents polyploidization and changes in calcium dynamics following stress with endothelin-1. Collectively, these results identify regulatory mechanisms of cardiac gene expression programs that modulate cardiomyocyte maturation, cellular stress response, and could serve as potential therapeutic targets.
Matching journals
The top 7 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- The long noncoding RNA Charme supervises cardiomyocyte maturation by controlling cell differentiation programs in the developing heart 97%
- Nr2f1a maintains atrial nkx2.5 expression to repress pacemaker identity within venous atrial cardiomyocytes 96%
- Dynamic effects of genetic variation on gene expression revealed following hypoxic stress in cardiomyocytes 96%
Similar papers in this journal
- Characterization of transcript enrichment and detection bias in single-nuclei RNA-seq for mapping of distinct human adipocyte lineages 93%
- Chromosome engineering to correct a complex rearrangement on Chromosome 8 reveals the effects of 8p syndrome on gene expression and neural differentiation 92%
- Functional Annotation of Human Long Non-Coding RNAs via Molecular Phenotyping 92%
Similar papers in this journal
- Minimal in vivo requirements for developmentally regulated cardiac long intergenic non-coding RNAs 97%
- Reduced TBX5 dosage undermines developmental control of atrial cardiomyocyte identity in a model of human atrial disease 96%
- Multi-modal refinement of the human heart atlas during the first gestational trimester 96%
Similar papers in this journal
- A microRNA program controls the transition of cardiomyocyte hyperplasia to hypertrophy and stimulates mammalian cardiac regeneration 95%
- The lncRNA Sweetheart regulates compensatory cardiac hypertrophy after myocardial injury 94%
- Single-cell transcriptome analysis reveals CD34 as a novel marker of human sinoatrial node pacemaker cardiomyocytes 94%
Similar papers in this journal
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.