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Epigenetic Regulation of Cardiac Myofibril Gene Expression During Heart Development

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Abstract

Cardiac gene expression regulation is controlled not only by genetic factors but also by environmental, i.e., epigenetic factors. Several environmental toxic effects such as oxidative stress and ischemia can result in abnormal myofibril gene expression during heart development. Troponin, one of the regulatory myofibril proteins in the heart, is a well-known model in study of cardiac gene regulation during the development. In our previous studies, we have demonstrated that fetal form troponin I (ssTnI) expression in the heart is partially regulated by hormones, such as thyroid hormone. In the present study, we have explored the epigenetic role of histone modification in the regulation of ssTnI expression. Mouse hearts were collected at different time of heart development, i.e., embryonic day 15.5, postnatal day 1, day 7, day 14 and day 21. Levels of histone H3 acetylation (acH3) and histone H3 lysine 9 trimethylation (H3K9me3) were detected using chromatin immunoprecipitation assays in slow upstream regulatory element (SURE) domain (TnI slow upstream regulatory element), 300-bp proximal upstream domain and the first intron of ssTnI gene, which are recognized as critical regions for ssTnI regulation. We found that the levels of acH3 on the SURE region were gradually decreased, corresponding to a similar decrease of ssTnI expression in the heart, whereas the levels of H3K9me3 in the first intron of ssTnI gene were gradually increased. Our results indicate that both histone acetylation and methylation are involved in the epigenetic regulation of ssTnI expression in the heart during the development, which are the targets for environmental factors.

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Acknowledgments

This study was supported in part by research grants from Natural Science Foundation of China (NSFC Grant Number: 31271218 to Xupei Huang).

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Authors and Affiliations

  1. Heart Centre, Children’s Hospital of Chongqing Medical University, Chongqing, People’s Republic of China

    Weian Zhao, Lingjuan Liu, Bo Pan, Yang Xu & Jie Tian

  2. Ministry of Education Key Laboratory of Child Development and Disorders, Key Laboratory of Pediatrics in Chongqing, CSTC2009CA5002, Chongqing International Science and Technology Cooperation Center for Child Development and Disorders, Chongqing, People’s Republic of China

    Lingjuan Liu & Jing Zhu

  3. Department of Biomedical Science, Charlie E. Schmidt College of Medicine, Florida Atlantic University, Boca Raton, FL, USA

    Changlong Nan & Xupei Huang

  4. Department of Cardiology, The Children’s Hospital of Chongqing Medical University, 136 Zhongshan 2nd Road, Yu Zhong District, Chongqing, 400014, People’s Republic of China

    Jie Tian

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  1. Weian Zhao
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  2. Lingjuan Liu
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  3. Bo Pan
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  4. Yang Xu
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  5. Jing Zhu
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  6. Changlong Nan
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  7. Xupei Huang
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  8. Jie Tian
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Correspondence to Jie Tian.

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Weian Zhao and Lingjuan Liu have contributed equally to this work.

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Zhao, W., Liu, L., Pan, B. et al. Epigenetic Regulation of Cardiac Myofibril Gene Expression During Heart Development. Cardiovasc Toxicol 15, 203–209 (2015). https://doi.org/10.1007/s12012-014-9278-7

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  • DOI: https://doi.org/10.1007/s12012-014-9278-7

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