DIFFERENTIAL METHYLATION OF THE GENES PAX8 AND GATA4 ALTERS THEIR EXPRESSION IN THE HEART DURING HYPERTROPHIC CARDIOMYOPATHY

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Hypertrophic cardiomyopathy (HCM) is the most common hereditary heart disease with a prevalence ranging from 1:500 to 1:200 individuals. The development and clinical presentation of HCM do not always conform to the traditional view of its monogenic inheritance pattern. One key to addressing this issue may lie in identifying epigenetic mechanisms regulating gene expression, particularly DNA methylation, involved in the pathogenesis of the disease and modifying its course. Utilizing previously obtained whole-genome data, we identified four extended genomic regions with reduced methylation levels in the myocardium of patients with HCM. These include region chr2:113993204-113994075 located within the transcribed area of the PAX8 gene, as well as three other regions – chr6:31148369-31148577, chr8:11565217-11567212, and chr8:22132791-22133357 – that are associated with promoters of genes PSORS1C3, GATA4, and PIWIL2, respectively. We were able to demonstrate altered expression of PAX8 and GATA4 genes containing one each of these four mentioned regions. Our findings will expand the currently very limited understanding of the unique features of epigenetic regulation in this condition.

作者简介

I. Kiselev

Federal State Budgetary Institution "National Medical Research Centre of Cardiology Named After Academician E.I. Chazov" of the Ministry of Health of the Russian Federation

Email: kiselev.ivan.1991@gmail.com
Moscow, Russian Federation

E. Dashtieva

Federal State Budgetary Institution "National Medical Research Centre of Cardiology Named After Academician E.I. Chazov" of the Ministry of Health of the Russian Federation

Moscow, Russian Federation

M. Pisklova

Federal State Budgetary Institution "National Medical Research Centre of Cardiology Named After Academician E.I. Chazov" of the Ministry of Health of the Russian Federation

Moscow, Russian Federation

O. Chumakova

Federal State Budgetary Institution "National Medical Research Centre of Cardiology Named After Academician E.I. Chazov" of the Ministry of Health of the Russian Federation

Moscow, Russian Federation

A. Zotov

Federal State Budgetary Institution "National Medical Research Centre of Cardiology Named After Academician E.I. Chazov" of the Ministry of Health of the Russian Federation

Moscow, Russian Federation

M. Kabilov

Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences

Novosibirsk, Russian Federation

O. Baturina

Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences

Novosibirsk, Russian Federation

D. Zateyshchikov

Federal State Budgetary Institution "National Medical Research Centre of Cardiology Named After Academician E.I. Chazov" of the Ministry of Health of the Russian Federation

Moscow, Russian Federation

O. Favorova

Federal State Budgetary Institution "National Medical Research Centre of Cardiology Named After Academician E.I. Chazov" of the Ministry of Health of the Russian Federation

Moscow, Russian Federation

参考

  1. Maron B.J., Desai M.Y., Nishimura R.A., et al. Management of Hypertrophic Cardiomyopathy: JACC State-of-the-Art Review // Journal of the American College of Cardiology. 2022. Vol. 79. N4. P. 390–414.
  2. Jansweijer J.A., van Spaendonck-Zwarts K.Y., Tanck M.W.T., et al. Heritability in Genetic Heart Disease: The Role of Genetic Background // Open Heart. 2019. Vol. 6. N1. Article ID e000929.
  3. Oliva-Sandoval M.J., Ruiz-Espejo F., Monserrat L., et al. Insights into Genotype-Phenotype Correlation in Hypertrophic Cardiomyopathy: Findings from 18 Spanish Families with a Single Mutation in MYBPC3 // Heart. 2010. Vol. 96. N24. P. 1980–1984.
  4. Maron B.J., Maron M.S., Maron B.A., et al. Moving Beyond the Sarcomere to Explain Heterogeneity in Hypertrophic Cardiomyopathy: JACC Review Topic of the Week // Journal of the American College of Cardiology. 2019. Vol. 73. N16. P. 1978–1986.
  5. Tadros R., Zheng S.L., Grace C., et al. Large-scale genome-wide association analyses identify novel genetic loci and mechanisms in hypertrophic cardiomyopathy // Nature Genetics. 2025. Vol. 57. N3. P. 530–538.
  6. Kiselev I., Kozin M., Baulina N., et al. Novel Genes Involved in Hypertrophic Cardiomyopathy: Data of Transcriptome and Methylene Profiling // International Journal of Molecular Sciences. 2022. Vol. 23. N23. Art. 15280.
  7. Glezeva N., Moran B., Collier P., et al. Targeted DNA Methylation Profiling of Human Cardiac Tissue Reveals Novel Epigenetic Traits and Gene Deregulation Across Different Heart Failure Patient Subtypes // Circulation: Heart Failure. 2019. Vol. 12, N3. Art. e005765.
  8. Elliott P.M., Anastasakis A., Borger M.A., et al. 2014 ESC Guidelines on Diagnosis and Management of Hypertrophic Cardiomyopathy: The Task Force for the Diagnosis and Management of Hypertrophic Cardiomyopathy of the European Society of Cardiology (ESC) // European Heart Journal. 2014. Vol. 35. No. 39. P. 2733–2779.
  9. Molina C.E., Jacquet E., Ponien P., et al. Identification of optimal reference genes for transcriptomic analyses in normal and diseased human heart // Cardiovascular Research. 2018. Vol. 114. N2. P. 247–258.
  10. Wu Y., Zhou X., Huang X., et al. Pax8 Plays a Pivotal Role in Regulation of Cardiomyocyte Growth and Senescence // Journal of Cellular and Molecular Medicine. 2016. Vol. 20. N3. P. 644–654.
  11. Yang D., Lai D., Huang X., et al. The Defects in Development and Apoptosis of Cardiomyocytes in Mice Lacking the Transcriptional Factor Pax-8 // International Journal of Cardiology. 2012. Vol. 154. N1. P. 43–51.
  12. Maitra M., Schluterman M.K., Nichols H.A., et al. Interaction of Gata4 and Gata6 with Tox5 Is Critical for Normal Cardiac Development // Developmental Biology. 2009. Vol. 326. N2. P. 368–377.
  13. Chen H., Zhou J., Chen H., et al. Bmi-1-RING1B Prevents GATA4-Dependent Senescence-Associated Pathological Cardiac Hypertrophy by Promoting Autophagic Degradation of GATA4 // Clinical and Translational Medicine. 2022. Vol. 12. N1. Art. e574.
  14. Shimizu S., Sunagawa Y., Hajika N., et al. Multimerization of the GATA4 Transcription Factor Regulates Transcriptional Activity and Cardiomyocyte Hypertrophic Response // International Journal of Biological Sciences. 2022. Vol. 18. N7. P. 1079–1095.
  15. Policiechio S., Washer S., Viana J., et al. Genome-Wide DNA Methylation Meta-Analysis in the Brains of Suicide Completers // Translational Psychiatry. 2020. Vol. 10. Art. 69.

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