ArticleCirculation research2017
Demethylation of H3K27 Is Essential for the Induction of Direct Cardiac Reprogramming by miR Combo.
Article in Circulation research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers, 1 of them a synthesis that pooled it.
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
73 citing papers in PubMed, 1 synthesis or guideline pooled it, 112 citations in OpenAlex.
- Cardiac Regeneration: New Insights Into the Frontier of Ischemic Heart Failure Therapy.Frontiers in bioengineering and biotechnology · 2020Pooled it
- The cardiac 4D nucleome: nuclear and chromatin dynamics across development, disease and ageing.Nature reviews. Cardiology · 2026Review
- Hemoglobin inhibits fibroblast-to-cardiomyocyte reprogramming via TLR2/TLR4-dependent chromatin compaction.Molecular therapy. Nucleic acids · 2026Article
- Sustained β-catenin activation via GSK3 inhibition promotes direct fibroblast-to-cardiomyocyte reprogramming.The Journal of biological chemistry · 2026Article
- Spatiotemporal precision interventions for cardiac repair and regenerative therapy.Experimental & molecular medicine · 2026Review
- The DNA Demethylase TET1 is a Pivotal Regulator of the miR-124/ISX9-Instructed Conversion of Astrocytes to Induced Neurons.Molecular neurobiology · 2026Article
- Enhancing cardiomyocyte reprogramming efficiency by targeting cellular senescence is mediated via Rb1 gene.Stem cell research & therapy · 2025Article
- Kdm7aa Orchestrates an Immunomodulatory Cardiomyocyte Program to Enable Zebrafish Heart Regeneration.International journal of molecular sciences · 2025Article
- In Vivo Targeted Reprogramming of Cardiac Fibroblasts for Heart Regeneration: Advances and Therapeutic Potential.Bioengineering (Basel, Switzerland) · 2025Review
- RNA Therapies in Cardio-Kidney-Metabolic Syndrome: Advancing Disease Management.Journal of cardiovascular translational research · 2025Review
- Role and research progress of histone modification in cardiovascular diseases (Review).Experimental and therapeutic medicine · 2025Review
- Investigating Müller glia reprogramming in mice: a retrospective of the last decade, and a look to the future.Neural regeneration research · 2025Article
- Cell reprogramming: methods, mechanisms and applications.Cell regeneration (London, England) · 2025Review
- Decoding the Epigenome of Breast Cancer.International journal of molecular sciences · 2025Review
- Putative Epigenetic Regulator microRNAs (epi-miRNAs) and Their Predicted Targets in High-Fat Diet-Induced Cardiac Dysfunction: An In Silico Analysis in Obese Rats.International journal of molecular sciences · 2025Article
- Nucleosome repositioning in cardiac reprogramming.PloS one · 2025Article
- H3K27me3 Loss in Central Nervous System Tumors: Diagnostic, Prognostic, and Therapeutic Implications.Cancers · 2024Review
- Direct Cardiac Reprogramming in the Age of Computational Biology.Journal of cardiovascular development and disease · 2024Review
- Disruption of G-quadruplex dynamicity by BRCA2 abrogation instigates phase separation and break-induced replication at telomeres.Nucleic acids research · 2024Article
- C166 EVs potentiate miR cardiac reprogramming via miR-148a-3p.Journal of molecular and cellular cardiology · 2024Article
13 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
rationaleDirect reprogramming of cardiac fibroblasts to cardiomyocytes has recently emerged as a novel and promising approach to regenerate the injured myocardium. We have previously demonstrated the feasibility of this approach in vitro and in vivo using a combination of 4 microRNAs (miR-1, miR-133, miR-208, and miR-499) that we named miR combo. However, the mechanism of miR combo mediated direct cardiac reprogramming is currently unknown.
objectiveHere, we investigated the possibility that miR combo initiated direct cardiac reprogramming through an epigenetic mechanism. METHODS AND
resultsUsing a quantitative polymerase chain reaction array, we found that histone methyltransferases and demethylases that regulate the trimethylation of H3K27 (H3K27me3), an epigenetic modification that marks transcriptional repression, were changed in miR combo-treated fibroblasts. Accordingly, global H3K27me3 levels were downregulated by miR combo treatment. In particular, the promoter region of cardiac transcription factors showed decreased H3K27me3 as revealed by chromatin immunoprecipitation coupled with quantitative polymerase chain reaction. Inhibition of H3K27 methyltransferases or of the PRC2 (Polycomb Repressive Complex 2) by pharmaceutical inhibition or siRNA reduced the levels of H3K27me3 and induced cardiogenic markers at the RNA and protein level, similarly to miR combo treatment. In contrast, knockdown of the H3K27 demethylases Kdm6A and Kdm6B restored the levels of H3K27me3 and blocked the induction of cardiac gene expression in miR combo-treated fibroblasts.
conclusionsIn summary, we demonstrated that removal of the repressive mark H3K27me3 is essential for the induction of cardiac reprogramming by miR combo. Our data not only highlight the importance of regulating the epigenetic landscape during cell fate conversion but also provide a framework to improve this technique.
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.