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Epigenetic memory: gene writer, eraser and homocysteine

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Abstract

Naturally chromatin remodeling is highly organized, consisting of histone acetylation (opening/relaxation of the compact chromatin structure), DNA methylation (inhibition of the gene expression activity) and sequence rearrangement by shifting. All this is essentially required for proper “in-printing and off-printing” of genes thus ensuring the epigenetic memory process. Any imbalance in ratios of DNA methyltransferase (DNMT, gene writer), fat-mass obesity-associated protein (FTO, gene eraser) and product (function) homocysteine (Hcy) could lead to numerous diseases. Interestingly, a similar process also happens in stem cells during embryogenesis and development. Despite gigantic unsuccessful efforts undertaken thus far toward the conversion of a stem cell into a functional cardiomyocyte, there has been hardly any study that shows successful conversion of a stem cell into a multinucleated cardiomyocyte. We have shown nuclear hypertrophy during heart failure, however; the mechanism(s) of epigenetic memory, regulation of genes during fertilization, embryogenesis, development and during adulthood remain far from understanding. In addition, there may be a connection of aging, loosing of the memory leading to death, and presumably to reincarnation. This review highlights some of these pertinent issues facing the discipline of biology as a whole today.

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Abbreviations

DAAM:

Disheveled-associated activator of morphogenesis

DNMT:

DNA methyltransferase

FTO:

Fat-mass obesity-associated protein

Hcy:

Homocysteine

Met:

Methionine

mTORC1:

Mechanistic target of rapamycin complex 1

NLRP3:

Nod-Like Receptor (NLR) Family Pyrin Domain Containing 3

PC:

Phosphatidylcholine

PCP:

Phosphatidylcholine phosphatase

PE:

Phosphatidylethanolamine

PEMT:

Phosphatidylethanolamine methyltransferase

REDD1:

Regulated in development DNA damage response 1

SAHH:

S-adenosine homocysteine hydrolase

SAM:

S-adenosine methionine; SAH

S-adenosine homocysteine:

TLR4, toll-like receptor-4

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Acknowledgements

The authors would like to thank all members of the laboratory for their continued help, and excellent support. Part of this study was supported by NIH grants AR-71789, HL139047, and DK116591.

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Authors and Affiliations

  1. Department of Physiology, University of Louisville School of Medicine, Louisville, KY, 40202, USA

    Suresh C. Tyagi, Dragana Stanisic & Mahavir Singh

  2. Department of Dentistry, Faculty of Medical Sciences, University of Kragujevac, 34000, Kragujevac, Serbia

    Dragana Stanisic

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Correspondence to Mahavir Singh.

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Tyagi, S.C., Stanisic, D. & Singh, M. Epigenetic memory: gene writer, eraser and homocysteine. Mol Cell Biochem 476, 507–512 (2021). https://doi.org/10.1007/s11010-020-03895-4

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