Epigenetic mechanisms in cardiac failure and recovery

Project Summary

Chronic heart failure constitutes the common end-stage of multiple cardiovascular diseases. We have established a dynamic map of DNA methylation, histone modifications and 3D chromatin structure of human cardiac myocytes during disease. Thus, the aim is to identify the epigenetic mechanisms involved in functional recovery of diseased cardiac myocytes. We propose to determine the functional relevance of DNA methylcytosine dioxygenases for establishment of the enhancer landscape of cardiac myocytes. We will determine the epigenome profiles of cardiac myocyte recovery in human terminal heart.

Selected project-relevant publications

• Ngo V., Fleischmann B.K., Jung M., Hein L. and Lother A. (2022) Histone Deacetylase 6 Inhibitor JS28 Prevents Pathological Gene Expression in Cardiac Myocytes. J Am Heart Assoc 11, e025857.
• Lother A., Bondareva O., Saadatmand A.R., Pollmeier L., Härdtner C., Hilgendorf I., Weichenhan D., Eckstein V., Plass C., Bode C., Backs J., Hein L. and Gilsbach R. (2021) Diabetes changes gene expression but not DNA methylation in cardiac cells. J Mol Cell Cardiol 151, 74-87.
• Rommel C. and Hein L. (2020) Four Dimensions of the Cardiac Myocyte Epigenome: from Fetal to Adult Heart. Curr Cardiol Rep 22, 26.
• Deng L., Pollmeier L., Zhou Q., Bergemann S., Bode C., Hein L. and Lother A. (2020) Gene expression in immortalized versus primary isolated cardiac endothelial cells. Sci Rep 10, 2241.
• Sheikh B.N., Bondareva O., Guhathakurta S., Tsang T.H., Sikora K., Aizarani N., Sagar, Holz H., Grün D., Hein L. and Akhtar A. (2019) Systematic Identification of Cell-Cell Communication Networks in the Developing Brain. iScience 21, 273-287.
• Lother A., Bergemann S., Kowalski J., Huck M., Gilsbach R., Bode C. and Hein L. (2018) Inhibition of the cardiac myocyte mineralocorticoid receptor ameliorates doxorubicin-induced cardiotoxicity. Cardiovasc Res 114, 282-290.
• Lother A., Bergemann S., Deng L., Moser M., Bode C. and Hein L. (2018) Cardiac Endothelial Cell Transcriptome. Arterioscler Thromb Vasc Biol 38, 566-574.
• Gilsbach R., Schwaderer M., Preissl S., Gruning B.A., Kranzhofer D., Schneider P., Nuhrenberg T.G., Mulero-Navarro S., Weichenhan D., Braun C., Dressen M., Jacobs A.R., Lahm H., Doenst T., Backofen R., Krane M., Gelb B.D. and Hein L. (2018) Distinct epigenetic programs regulate cardiac myocyte development and disease in the human heart in vivo. Nat Commun 9, 391.
• Nothjunge S., Nuhrenberg T.G., Gruning B.A., Doppler S.A., Preissl S., Schwaderer M., Rommel C., Krane M., Hein L. and Gilsbach R. (2017) DNA methylation signatures follow preformed chromatin compartments in cardiac myocytes. Nat Commun 8, 1667.
• Kranzhofer D.K., Gilsbach R., Gruning B.A., Backofen R., Nuhrenberg T.G. and Hein L. (2016) 5′-Hydroxymethylcytosine Precedes Loss of CpG Methylation in Enhancers and Genes Undergoing Activation in Cardiomyocyte Maturation. PLoS One 11, e0166575.
• Chatterjee A., Seyfferth J., Lucci J., Gilsbach R., Preissl S., Bottinger L., Martensson C.U., Panhale A., Stehle T., Kretz O., Sahyoun A.H., Avilov S., Eimer S., Hein L., Pfanner N., Becker T. and Akhtar A. (2016) MOF Acetyl Transferase Regulates Transcription and Respiration in Mitochondria. Cell 167, 722-738.e723.
• Mayer S., Gilsbach R., Preissl S., Monroy Ordonez E.B., Schnick T., Beetz N., Lother A., Rommel C., Ihle H.M., Bugger H., Ruhle F., Schrepper A., Schwarzer M., Heilmann C., Bonisch U., Gupta S.K., Wilpert J., Kretz O., Von Elverfeldt D., Orth J., Aktories K., Beyersdorf F., Bode C., Stiller B., Kruger M., Thum T., Doenst T., Stoll M. and Hein L. (2015) Adrenergic Repression of the Epigenetic Reader MeCP2 Facilitates Cardiac Adaptation in Chronic Heart Failure. Circ Res
• Preissl S., Schwaderer M., Raulf A., Hesse M., Gruning B.A., Kobele C., Backofen R., Fleischmann B.K., Hein L. and Gilsbach R. (2015) Deciphering the Epigenetic Code of Cardiac Myocyte Transcription. Circ Res 117, 413-423.
• Nuhrenberg T.G., Hammann N., Schnick T., Preissl S., Witten A., Stoll M., Gilsbach R., Neumann F.J. and Hein L. (2015) Cardiac Myocyte De Novo DNA Methyltransferases 3a/3b Are Dispensable for Cardiac Function and Remodeling after Chronic Pressure Overload in Mice. PLoS One 10, e0131019.
• Gilsbach R., Preissl S., Gruning B.A., Schnick T., Burger L., Benes V., Wurch A., Bonisch U., Gunther S., Backofen R., Fleischmann B.K., Schubeler D. and Hein L. (2014) Dynamic DNA methylation orchestrates cardiomyocyte development, maturation and disease. Nat Commun 5, 5288.