ArticleCell reports2019
Hand2 Selectively Reorganizes Chromatin Accessibility to Induce Pacemaker-like Transcriptional Reprogramming.
Article in Cell reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 34 citations in OpenAlex.
- Rare TruncatingGenes · 2026Article
- Targeting Cardiac Fibroblast Plasticity for Antifibrotic and Regenerative Therapy in Heart Failure.Cells · 2026Review
- Functional architecture of cardiac TF regulatory landscapes in control of mammalian heart development.bioRxiv : the preprint server for biology · 2025Article
- PITX2 dosage-dependent changes in pacemaker cell state underlie sinus node dysfunction and atrial arrhythmias.Nature communications · 2025Article
- HAND2 invades nucleolar condensates to pioneer lineage-specific cardiac pacemaker gene programs.Nature communications · 2025Article
- Active repression of cell fate plasticity by PROX1 safeguards hepatocyte identity and prevents liver tumorigenesis.Nature genetics · 2025Article
- The 3' region of the ZPA regulatory sequence (ZRS) is required for activity and contains a critical E-box.Frontiers in cell and developmental biology · 2025Article
- Chromatin accessibility: biological functions, molecular mechanisms and therapeutic application.Signal transduction and targeted therapy · 2024Review
- A gene desert required for regulatory control of pleiotropic Shox2 expression and embryonic survival.Nature communications · 2024Article
- Can we stop one heart from breaking: triumphs and challenges in cardiac reprogramming.Current opinion in genetics & development · 2023Review
- Global chromatin landscapes identify candidate noncoding modifiers of cardiac rhythm.The Journal of clinical investigation · 2023Article
- Article
- The HASTER lncRNA promoter is a cis-acting transcriptional stabilizer of HNF1A.Nature cell biology · 2022Article
- Generation of a recombinant version of a biologically active cell-permeant human HAND2 transcription factor from E. coli.Scientific reports · 2022Article
- A review of protocols for human iPSC culture, cardiac differentiation, subtype-specification, maturation, and direct reprogramming.STAR protocols · 2022Review
- Neonatal Deletion ofJournal of cardiovascular development and disease · 2022Article
- Patient-Specific TBX5-G125R Variant Induces Profound Transcriptional Deregulation and Atrial Dysfunction.Circulation · 2022Article
- Editorial: Cardiac Pacemaking in Health and Disease: From Genes to Function.Frontiers in physiology · 2022Article
- Review
- Molecular Profiling of the Cardiac Conduction System: the Dawn of a New Era.Current cardiology reports · 2021Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Gata4, Hand2, Mef2c, and Tbx5 (GHMT) can reprogram transduced fibroblasts into induced pacemaker-like myocytes (iPMs), but the underlying mechanisms remain obscure. Here, we explore the role of Hand2 in iPM formation by using a combination of transcriptome, genome, and biochemical assays. We found many shared transcriptional signatures between iPMs and the endogenous sinoatrial node (SAN), yet key regulatory networks remain missing. We demonstrate that Hand2 augments chromatin accessibility at loci involved in sarcomere organization, electrical coupling, and membrane depolarization. Focusing on an established cardiac Hand2 cistrome, we observe selective reorganization of chromatin accessibility to promote pacemaker-specific gene expression. Moreover, we identify a Hand2 cardiac subtype diversity (CSD) domain through biochemical analysis of the N terminus. By integrating our RNA-seq and ATAC-seq datasets, we highlight desmosome organization as a hallmark feature of iPM formation. Collectively, our results illuminate Hand2-dependent mechanisms that may guide future efforts to rationally improve iPM formation.
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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.