ArticleClinical epigenetics2021
Multi-omics integration identifies key upstream regulators of pathomechanisms in hypertrophic cardiomyopathy due to truncating MYBPC3 mutations.
Article in Clinical epigenetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
22 citing papers in PubMed, 34 citations in OpenAlex.
- Mavacamten shows broad benefit in human and mouse models of MYBPC3-related hypertrophic cardiomyopathy.Nature cardiovascular research · 2026Article
- Integrative Bioinformatics Analyses Reveal X Chromosome Inactivation Escape Genes Dosage Dysregulation Is the Primary Contributor to Turner Syndrome.Iranian journal of biotechnology · 2026Article
- Astragaloside IV inhibits the progression of hypertensive heart disease via the RXRA/PPARG/SIRT3 axis.Journal of molecular medicine (Berlin, Germany) · 2025Article
- Signaling pathway alterations in hearts of a porcine model harboring a β-myosin heavy chain (MYH7-R403Q) gene variant.Journal of molecular and cellular cardiology plus · 2025Article
- Role and research progress of histone modification in cardiovascular diseases (Review).Experimental and therapeutic medicine · 2025Review
- The Role of Signalling Pathways in Myocardial Fibrosis in Hypertrophic Cardiomyopathy.Reviews in cardiovascular medicine · 2025Review
- Integrative analysis of transcriptome, DNA methylome, and chromatin accessibility reveals candidate therapeutic targets in hypertrophic cardiomyopathy.Protein & cell · 2024Article
- Deciphering metabolomics and lipidomics landscape in zebrafish hypertrophic cardiomyopathy model.Scientific reports · 2024Article
- Studying Pathogenetic Contribution of a Variant of Unknown Significance, p.M659I (c.1977G > A) in MYH7, to the Development of Hypertrophic Cardiomyopathy Using CRISPR/Cas9-Engineered Isogenic Induced Pluripotent Stem Cells.International journal of molecular sciences · 2024Article
- Using Omics to Identify Novel Therapeutic Targets in Heart Failure.Circulation. Genomic and precision medicine · 2024Review
- A Multimodal Omics Framework to Empower Target Discovery for Cardiovascular Regeneration.Cardiovascular drugs and therapy · 2024Review
- Transcriptome analysis of human hypertrophic cardiomyopathy reveals inhibited cardiac development pathways in children.iScience · 2024Article
- Hypertrophic cardiomyopathy inThe journal of cardiovascular aging · 2024Article
- Circulating Acylcarnitines Associated with Hypertrophic Cardiomyopathy Severity: an Exploratory Cross-Sectional Study in MYBPC3 Founder Variant Carriers.Journal of cardiovascular translational research · 2023Article
- Myocardial Fibrosis in Hypertrophic Cardiomyopathy: A Perspective from Fibroblasts.International journal of molecular sciences · 2023Review
- Untargeted Metabolomics Identifies Potential Hypertrophic Cardiomyopathy Biomarkers in Carriers ofInternational journal of molecular sciences · 2023Article
- Targeting lipid metabolism as a new therapeutic strategy for inherited cardiomyopathies.Frontiers in cardiovascular medicine · 2023Review
- Transcriptome data analysis of primary cardiomyopathies reveals perturbations in arachidonic acid metabolism.Frontiers in cardiovascular medicine · 2023Article
- Novel Genes Involved in Hypertrophic Cardiomyopathy: Data of Transcriptome and Methylome Profiling.International journal of molecular sciences · 2022Article
- Timing of Blood Sample Processing Affects the Transcriptomic and Epigenomic Profiles in CD4Cells · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
28 authors at 7 institutions in 3 countries.
Funding
Abstract
backgroundHypertrophic cardiomyopathy (HCM) is the most common genetic disease of the cardiac muscle, frequently caused by mutations in MYBPC3. However, little is known about the upstream pathways and key regulators causing the disease. Therefore, we employed a multi-omics approach to study the pathomechanisms underlying HCM comparing patient hearts harboring MYBPC3 mutations to control hearts.
resultsUsing H3K27ac ChIP-seq and RNA-seq we obtained 9310 differentially acetylated regions and 2033 differentially expressed genes, respectively, between 13 HCM and 10 control hearts. We obtained 441 differentially expressed proteins between 11 HCM and 8 control hearts using proteomics. By integrating multi-omics datasets, we identified a set of DNA regions and genes that differentiate HCM from control hearts and 53 protein-coding genes as the major contributors. This comprehensive analysis consistently points toward altered extracellular matrix formation, muscle contraction, and metabolism. Therefore, we studied enriched transcription factor (TF) binding motifs and identified 9 motif-encoded TFs, including KLF15, ETV4, AR, CLOCK, ETS2, GATA5, MEIS1, RXRA, and ZFX. Selected candidates were examined in stem cell-derived cardiomyocytes with and without mutated MYBPC3. Furthermore, we observed an abundance of acetylation signals and transcripts derived from cardiomyocytes compared to non-myocyte populations.
conclusionsBy integrating histone acetylome, transcriptome, and proteome profiles, we identified major effector genes and protein networks that drive the pathological changes in HCM with mutated MYBPC3. Our work identifies 38 highly affected protein-coding genes as potential plasma HCM biomarkers and 9 TFs as potential upstream regulators of these pathomechanisms that may serve as possible therapeutic targets.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.