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Cited by 39Congenital heart defects researchGenetics and Neurodevelopmental DisordersCardiac electrophysiology and arrhythmias

Disturbance of cardiac gene expression and cardiomyocyte structure predisposes Mecp2-null mice to arrhythmias

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Hara, Munetsugu, Takahashi, Tomoyuki, Mitsumasu, Chiaki, Igata, Sachiyo, Takano, Makoto, Minami, Tomoko, Yasukawa, Hideo, Okayama, Satoko +7 more·2015·Scientific Reports
DOI 10.1038/srep11204PMC PMC4466896
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Abstract

Methyl-CpG-binding protein 2 (MeCP2) is an epigenetic regulator of gene expression that is essential for normal brain development. Mutations in MeCP2 lead to disrupted neuronal function and can cause Rett syndrome (RTT), a neurodevelopmental disorder. Previous studies reported cardiac dysfunction, including arrhythmias in both RTT patients and animal models of RTT. In addition, recent studies indicate that MeCP2 may be involved in cardiac development and dysfunction, but its role in the developing and adult heart remains unknown. In this study, we found that Mecp2-null ESCs could differentiate into cardiomyocytes, but the development and further differentiation of cardiovascular progenitors were significantly affected in MeCP2 deficiency. In addition, we revealed that loss of MeCP2 led to dysregulation of endogenous cardiac genes and myocardial structural alterations, although Mecp2-null mice did not exhibit obvious cardiac functional abnormalities. Furthermore, we detected methylation of the CpG islands in the Tbx5 locus and showed that MeCP2 could target these sequences. Taken together, these results suggest that MeCP2 is an important regulator of the gene-expression program responsible for maintaining normal cardiac development and cardiomyocyte structure.

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  • Both RTT patients and Mecp2 mutant mice present with metabolic syndrome, oxidative stress, cardiac defects, decreased bone density and urological dysfunction.

    “Additionally, both RTT patients and Mecp2 mutant mice present with metabolic syndrome [15,180], oxidative stress [27,29], cardiac defects [211,212], decreased bone density [174,213] and urological dysfunction [214,215].”

    From Rett syndrome: a neurological disorder with metabolic components (2018) · cites this paper as [211]

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Authors
Hara, M., Takahashi, T., Mitsumasu, C., Igata, S., Takano, M., Minami, T., Yasukawa, H., Okayama, S., Nakamura, K., Okabe, Y., Tanaka, E., Takemura, G., Kosai, K.-I., Yamashita, Y., & Matsuishi, T.
Affiliations
  • Kurume University (JP)
  • Asahi University (JP)
Corresponding author
Takahashi, Tomoyuki
ORCID
Venue
Scientific Reports
Publisher
Springer Science and Business Media LLC
Published
2015-06-15
Volume
5
Issue
1
Pages
11204-11204
ISSN
2045-2322 (ISSN-L)
DOI
10.1038/srep11204
PMC
PMC4466896
OpenAlex
W2265047658
Cited by
39
References
1
Citations by year
2026: 4 · 2025: 5 · 2024: 1 · 2023: 6 · 2022: 6 · 2021: 3 · 2020: 1 · 2019: 6 · 2018: 2 · 2017: 3 · 2016: 2
FWCI
1.01
Type
journal article
Language
en
Open access
Licence
Locations
  • Scientific Reports (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • Ishibashi Foundation
  • Japan Society for the Promotion of Science (26670292, 24300145)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Congenital heart defects research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
Keywords
MeCP2, Rett syndrome, cardiac arrhythmias, cardiomyocyte differentiation, heart development, epigenetic regulation, CpG island methylation, TBX5, Mecp2-null mice, embryonic stem cells, cardiovascular progenitors, myocardial structure, gene expression dysregulation
MeSH terms
Animals, Arrhythmias, Cardiac, Cell Differentiation, Disease Models, Animal, Female, Humans, Myocardium, Myosins, Signal Transduction, Mice, Knockout, CpG Islands, DNA Methylation, Genetic Predisposition to Disease, T-Box Domain Proteins, Gene Expression Profiling, Myocytes, Cardiac, Epigenesis, Genetic, Mice, Methyl-CpG-Binding Protein 2, Embryonic Stem Cells

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