The ability to silence or promote gene expression. Epigenetics is an extra layer of regulation above the genomic content itself that enables genes to be turned on/off.

Epigenetics tries to understand the mechanisms by which genes are “turned” on and off. With 20,000+ genes we have, understanding what might result from different combinations of genes being turned on or off, and subsequent interactions between various components of the outcome, is at present largely an educated or perhaps inspired guess. It is a pipe dream that a complete understanding of this might possibly cure diseases...

The availability of human genomic and associated clinical data has generated numerous genetic association studies that further validate the importance of identifying patterns of genetic variation and/or specific mutational changes in both predicting and in signaling disease onset. Although it is known that specific heritable DNA mutations may be associated with disease, many diseases currently do not provide a 'red flag' of consistent mutations capable of fully predicting illness or illuminating a clear path for therapeutic discovery. It is becoming more evident that epigenetic modifications including DNA methylation, histone acetylation, and posttranslational modifications of proteins involved in gene expression impact pathways participating in disease onset and thus may serve as early disease stage biomarker in addition to or even in the absence of specific heritable DNA mutations. While it established that epigenetic modification of DNA has the power to modulate expression of genes vital in developmental and life-sustaining processes, we are now realizing the potential impact of altered epigenetic profiles resulting from individual environmental exposures. This realization has prompted investigations to examine not only the consequences of epigenetic change (e.g. disease) but to understand which upstream pathways may lead to the epigenetic change itself. For example, a recent study in Cancer Cell (Vaz et al. 2017) demonstrated that chronic exposure of human bronchial epithelial cells to cigarette smoke led to aberrant DNA methylation and silencing of genes that typically inhibit pathways found associated with lung cancer. Such studies of epigenetic modification provide potential targets for therapeutic action perhaps even before disease onset. Therapy targeting epigenetic modifications (e.g. histone deacetylase inhibitors or HDACi) is currently being used with variable success. Invariably study of both heritable genetic changes and epigenetic modification have great potential to serve as biomarker for disease, perhaps illuminating pathways involved in disease initiation. Investigation of such epigenetic modifications including those associated with environmental exposures can provide possible target(s) for safe, effective therapeutic action where perhaps none existed before.


Vaz M, Hwang S, Kagiampakis I, Phallen J, Patil A, O’Hagan H, Murphy L, Zahnow C, Gabrielson E, Velculescu V, et al. 2017. Chronic Cigarette Smoke-Induced Epigenomic Changes Precede Sensitization of Bronchial Epithelial Cells to Single-Step Transformation by KRAS Mutations. Cancer Cell 32: 360–376.

Sometimes, greater than genetic modification.
Unfortunately, if one sticks to the strict definition of epigenetic as trans-generational inheritance not involving changes in the DNA sequence, there is a long way to go until we understand it. How do cells copy the modifications of each and every histone every time they divide? And how does the Dutch famine result in higher predisposition to obesity in subsequent generations?