Research Topic

Potential of Epigenetic Therapies in non-cancerous conditions

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It has become increasingly clear that aberrant epigenetic regulatory mechanisms are a major element not only in cancer [1] but also in the setting of non-cancerous disease. ...

It has become increasingly clear that aberrant epigenetic regulatory mechanisms are a major element not only in cancer [1] but also in the setting of non-cancerous disease.
Epigenetics originally invoked the notion of stable and heritable gene expression changes that are not due to changes in the primary DNA sequence. Two levels of epigenetic gene regulation can now be envisaged: the classic form involving stable heritable changes and enhanced epigenetic modifications, which can be regarded as regulatory mechanisms orchestrating inducible responses at the cellular level which may or may not be heritable. Current epigenetic mechanisms involve the following: DNA CpG methylation, histone post-translational modifications (PTMs), histone variants, and noncoding RNA (ncRNA). Aberrant epigenetic regulation of gene expression is now known to be important in the pathogenesis of various diseases, including cancer [2].
For example, while it is well established that mutations exist in the epigenetic machinery in cancer [3], it is often overlooked that mutations in proteins such as Maturity onset diabetes of the young (MODY) can affect their ability to bind to the epigenetic regulatory machinery [4], while mutant Huntingtin protein can disrupt the nuclear localization of KAT3A (CBP) [5], or affect histone ubiquitination [6].
As such disruption of appropriate epigenetic regulation of gene expression plays critical roles within the non-cancerous setting. This has implications in many areas of human health including metabolism, immunity, reproduction and aging.
Dysregulated epigenetic regulation may therefore lead to an increased risk of disease/ill health including lupus, diabetes, multiple sclerosis and other neurodegenerative conditions [4-8]. As such targeting the epigenetic machinery in health and disease may have either preventative or direct benefit in the treatment of many illnesses/diseases outside of the cancer setting. Examples of such include the potential to increase insulin sensitivity (9), activate latent viruses for clearance by existing anti-viral therapies (10), or alleviate symptoms of diseases such as arthritis (11) or enhance production/generation of biologically relevant stem cells for therapeutic purposes (12).
Clearly dysregulated epigenetics is not restricted to cancer. This Research Topic will explore the evidence for and therapeutic potential of targeting the epigenome within non-cancerous settings.

References
1. Baylin SB, Jones PA. (2011). Nat Rev Cancer. 11(10):726-34.
2. Teperino R, Lempradl A, Pospisilik JA. (2013). Cell Mol Life Sci. 70(9):1609-21.
3. Dawson MA, Kouzarides T. (2012). Cell. 150(1):12-27.
4. Gray, SG and DeMeyts, P. (2005). Diabetes Metab Res Rev. 21(5):416-33.
5. Gray SG. (2011). Epigenomics. 3(4):431-50.
6. Gray SG. (2011). Clin Epigenetics. 2(2):257-77.
7. Gray SG, Dangond F. (2006). Epigenetics. 1(2):67-75.
8. Gray SG (2013). Arthritis Res Ther. 15(2):207.
9. Xiao C, Giacca A, Lewis GF. (2011). Diabetes. 60(3):918-24.
10. Liang Y, et al. (2013). Sci Transl Med. 5(167):167ra5.
11. Vojinovic J, et al. (2011). Arthritis Rheum. 63(5):1452-8.
12. Papp B, Plath K. (2013). Cell. 152(6):1324-43.


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