ArticleDisease models & mechanisms2016
Cardiomyocyte-specific conditional knockout of the histone chaperone HIRA in mice results in hypertrophy, sarcolemmal damage and focal replacement fibrosis.
Article in Disease models & mechanisms, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 24 citations in OpenAlex.
- HIRA-mediated H3.3 deposition preserves hepatocyte cell identity during liver aging.Research square · 2026Article
- S100A10 knockdown exacerbates phenylephrine-induced cardiomyocyte hypertrophy via modulating mitochondrial oxidative phosphorylation.Frontiers in genetics · 2025Article
- Polyploidy and Myc Proto-Oncogenes Promote Stress Adaptation via Epigenetic Plasticity and Gene Regulatory Network Rewiring.International journal of molecular sciences · 2022Review
- Nucleosome proteostasis and histone turnover.Frontiers in molecular biosciences · 2022Review
- The roles and mechanisms of epigenetic regulation in pathological myocardial remodeling.Frontiers in cardiovascular medicine · 2022Review
- Nuclear deformation guides chromatin reorganization in cardiac development and disease.Nature biomedical engineering · 2021Article
- Epigenetic Regulation of Myogenesis: Focus on the Histone Variants.International journal of molecular sciences · 2021Review
- Synaptic and Gene Regulatory Mechanisms in Schizophrenia, Autism, and 22q11.2 Copy Number Variant-Mediated Risk for Neuropsychiatric Disorders.Biological psychiatry · 2020Article
- Epigenetics in Cardiac Hypertrophy and Heart Failure.JACC. Basic to translational science · 2019Review
- Metabolic Stress and Cardiovascular Disease in Diabetes Mellitus: The Role of ProteinArteriosclerosis, thrombosis, and vascular biology · 2019Review
- In the line-up: deleted genes associated with DiGeorge/22q11.2 deletion syndrome: are they all suspects?Journal of neurodevelopmental disorders · 2019Review
- HIRA directly targets the enhancers of selected cardiac transcription factors during in vitro differentiation of mouse embryonic stem cells.Molecular biology reports · 2018Article
- Reproducibility of histopathological findings in experimental pathology of the mouse: a sorry tail.Lab animal · 2017Article
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
HIRA is the histone chaperone responsible for replication-independent incorporation of histone variant H3.3 within gene bodies and regulatory regions of actively transcribed genes, and within the bivalent promoter regions of developmentally regulated genes. The HIRA gene lies within the 22q11.2 deletion syndrome critical region; individuals with this syndrome have multiple congenital heart defects. Because terminally differentiated cardiomyocytes have exited the cell cycle, histone variants should be utilized for the bulk of chromatin remodeling. Thus, HIRA is likely to play an important role in epigenetically defining the cardiac gene expression program. In this study, we determined the consequence of HIRA deficiency in cardiomyocytes in vivo by studying the phenotype of cardiomyocyte-specific Hira conditional-knockout mice. Loss of HIRA did not perturb heart development, but instead resulted in cardiomyocyte hypertrophy and susceptibility to sarcolemmal damage. Cardiomyocyte degeneration gave way to focal replacement fibrosis and impaired cardiac function. Gene expression was widely altered in Hira conditional-knockout hearts. Significantly affected pathways included responses to cellular stress, DNA repair and transcription. Consistent with heart failure, fetal cardiac genes were re-expressed in the Hira conditional knockout. Our results suggest that transcriptional regulation by HIRA is crucial for cardiomyocyte homeostasis.
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Registered trials
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