Mateen, BA; Hill, CS; Biddie, SC; Menon, DK; (2017) DNA Methylation: Basic Biology and Application to Traumatic Brain Injury. Journal of Neurotrauma , 34 (16) pp. 2379-2388. 10.1089/neu.2017.5007.

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Abstract

This article reviews the literature pertinent to epigenetic changes, and in particular, DNA methylation following traumatic brain injury (TBI). TBI is a heterogeneous disease that is a major cause of death and long-term disability. The links between TBI and epigenetics, the process by which environmental factors alter gene expression without changing the underlying DNA sequence, is an expanding area of research that may have profound consequences for understanding the disease, and for clinical care. There are various epigenetic changes that may occur as a direct result of TBI, including DNA methylation, histone modification, and changes in the levels of non-coding RNA. This review focuses on DNA methylation, its potential to alter the degree of injury, and the extent of recovery, including development of post-traumatic neurodegeneration, response to therapies, and the hereditable consequences of injury. The functional consequences of non-coding RNA and histone modifications are well described in the literature; however, the mechanism by which these three mechanisms interact are often overlooked. Here, we briefly describe the interaction of DNA methylation with the two other key epigenetic changes, and highlight key work being performed to understand the functional relevance of those mechanisms. The field of epigenetics is rapidly advancing as a result of the advent of less invasive and more versatile methods for measuring epigenetic proteins and their functional impact on cells; however, the evidence specific to TBI is limited. This review identifies several important outstanding questions that remain from the work already conducted, and highlights directions for the future. Traumatic Brain Injury (TBI) is heterogeneous disease that is a major cause of death and long-term disability. More than half of serious head trauma survivors may be moderately to severely disabled 1 year post-injury, and long-term impairments resulting from mild repetitive TBI are increasingly being recognized.1 Therefore, with incidence rates of >100 per 100,000 people, TBI is an important public health concern and requires further exploration.2 Recent efforts to understand disease pathophysiology have focused on epigenetics, the process by which environmental factors alter gene expression without changing the underlying DNA sequence. Epigenetic changes are increasingly implicated in the pathophysiology following TBI (Fig. 1),3 and may provide targets for therapy. This review seeks to provide an introduction to epigenetics, and focuses on specific aspects of the process as a context for understanding emerging publications on epigenetic changes in TBI.

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