Epigenetics is a relatively new field born from two parent sciences: genetics and developmental biology.  The prefix epi- means “above” or “in addition to.”  In order to understand what epigenetics is “in addition to,” or what it is “above,” we must meet its parent sciences.
Developmental biology is the study of how organisms grow and develop across their lives, from conception through the many changes that come with advanced age (senescence).
Figure 1. The human body undergoes many changes across the lifespan, from conception through older adulthood.
Multicellular organisms, such as human beings, begin as single cells. These single cells multiply and diverge from each other many times to form tissues and organs with unique characteristics.
Figure 2. At an early stage of human development (blastocyst), each cell has the potential to become many different kinds of tissue (pluripotency), which are incorporated into many different organs. Over the course of development, these cells navigate down different paths to become, for example, brain cells, bone cells, and heart cells. Most, but not all, of the cells in the human adult body have lost the ability to transform into other cell types and instead maintain a stable identity.
These tissues and organs work together to respond to the environment, and to each other, in a vast and complex system. In order for an organism to survive, this system must constantly work to repair itself and maintain equilibrium, while remaining flexible enough to endure or adapt to fluctuations introduced by its surroundings. Certain environmental conditions introduced at key times or over a long duration can have dramatic effects on the biological development of human beings.
Genetics is the study of the biological material called deoxyribonucleic acid (DNA), its contents, its structure, its function, and its transmission across generations through heredity.
Figure 3. DNA is like a recipe book for the human body. This “recipe” is somewhat flexible, but, like the real thing, ingredients generally need to be balanced and timing is critical.
We do not yet understand the function of all our DNA. Some parts of our DNA act as a repository for genes. Genes signal the body to make certain compounds (usually proteins) in a highly coordinated fashion. Other parts of our DNA contain directions about how and when to read the instructions called genes. The sum total of an organism’s DNA, including all of its genes, is called a genome. Although all parts of the body (usually) contain the same genome, specialized tissues and organs have restricted access to different parts of the genome at different times. For example, genes solely related to the function of the skeletal system are accessed by the cells that make up bones and not by the cells that make up the heart.
Epigenetics is the study of changes above the level of the genome. These changes do not affect the underlying content of the DNA; the recipes encoded by the genes remain the same. Instead, epigenetic changes alter the genome’s superstructure, or its architecture, in a way that impacts how the genome functions. By altering the genomic architecture, epigenetic changes can restrict a cell’s access to just those genes that are relevant to the cell’s purpose in the body. Epigenetics explains how cells in disparate tissues and organs can have the same genome, but look and act completely differently. By making small adjustments to the architecture of a genome, epigenetic changes give human beings the flexibility they need to develop from a single cell to a complex multi-cellular organism, and to continue responding to a dynamic environment across the lifespan.
Human DNA is (with few exceptions) not “edited” by one’s environment. The epigenome, on the other hand, is responsive to environmental changes across a lifetime. Changes in the epigenome are a normal part of life course development, but they have also been associated with certain health problems, such as type 2 diabetes and cancer. Some epigenetic changes can even be passed down from parents to their children.
Figure 4. Epigenetic changes occur “on top of” the genome, but do not change the underlying DNA.
Historically, there has been debate over the official definition of “epigenetics.” Most of this debate has centered on the issue of heritability. Cold Spring Harbor and the NIH Roadmap Epigenomics Mapping Consortium represent two respected institutions whose definitions of epigenetics are at odds with each other:
|Cold Spring Harbor conference consensus: Strict definition of epigenetics|
|An epigenetic trait is a stably heritable phenotype resulting from changes in a chromosome without alterations in the DNA sequence.|
|NIH Roadmap Epigenomics project scope: Inclusive definition of epigenetics|
|[…] epigenetics refers to both heritable changes in gene activity and expression (in the progeny of cells or of individuals) and also stable, long-term alterations in the transcriptional potential of a cell that are not necessarily heritable.|
Stricter definitions of epigenetics, like Cold Spring Harbor’s, require epigenetic changes to be heritable across cell divisions (mitotically), across generations of an organism (meiotically), or both. More inclusive definitions of epigenetics, like the NIH Roadmap Epigenomics Mapping Consortium’s, do not require modifications to be heritable, but suggest that they should have long-term effects on gene expression (when a gene is “turned on” and to what degree). The argument over heritable vs. non-heritable changes is important because its resolution determines which types of modifications are ultimately considered “epigenetic” and which fall into the more general category of “biochemical regulation.” For the purpose of this tutorial, we will rely on the more liberal definition provided by the NIH Roadmap Epigenomics Mapping Consortium. The consequence is that not all scientists will agree that each of the mechanisms described in this tutorial is necessarily “epigenetic.” Throughout the tutorial, we will use a note to mark wherever different definitions of epigenetics might cause a conflict in interpretation.
Epigenetics has built bridges between the fields of genetics and developmental biology, and has continued to grow new connections across disciplines, including psychology, epidemiology, neuroscience, nutrition, and many others. As the line between disciplines continues to blur, epigenetics is an increasingly useful tool for both bioscientists and social scientists. To gain a deeper understanding of epigenetic mechanisms and their impact on the human condition, a working knowledge of gene expression and genome structure are helpful:
Others might wish to skip directly to epigenetic regulation or an example of epigenetic effects on human wellbeing:
 Holliday, R. Epigenetics: A historical overview. Epigenetics 1, 76–80 (2006).
 Harper, D. Online Etymology Dictionary. (2014). at <http://www.etymonline.com>
 Pinney, S. E. & Simmons, R. a. Epigenetic mechanisms in the development of type 2 diabetes. Trends Endocrinol. Metab. 21, 223–9 (2010).
 Esteller, M. Epigenetics in cancer. N. Engl. J. Med. 358, 1148–59 (2008).
 Berger, S. L., Kouzarides, T., Shiekhattar, R. & Shilatifard, A. An operational definition of epigenetics. Genes Dev. 23, 781–3 (2009).
 NIH Roadmap Epigenomics. Roadmap Epigenomics Project – Overview. (2010). at <http://www.roadmapepigenomics.org/overview>
Teaching / Learning Materials
- U. of Utah Genetic Science Learning Center: Epigenetics Multimedia
- NOVA ScienceNow: Epigenetics with Dr. Randy L. Jirtle (Video)
- NHGRI Fact Sheet: Epigenomics
- NCBI Bookshelf: Epigenomics Help – Epigenomics Scientific Background
- Geneimprint: Gateway to gene imprinting information
- EpiGenie Science Writers
- Scitable by Nature Education: Genetics Topic Room
Organizations and Landmark Projects
- International Human Epigenome Consortium
- NIH Roadmap Epigenomics Project
- ENCODE Project: Encyclopedia of DNA Elements
- NHGRI: National Human Genome Research Institute
- NIH Epigenomics Program
- NCHPEG BSSR: Genetics and Social Science – Expanding Transdisciplinary Research
Scholarly Review Articles
- Enivronmental epigenomics and disease susceptibility Jirtle R. and Skinner M., Nat Rev Genet (2007) 8(4):253-62 doi: 10.1038/nrg2045
- Epigenetics, chromatin and genome organization: recent advances from the ENCODE project Siggens L. and Ekwall K., J Intern Med (2014) doi: 10.1111/joim.12231
- Epigenetics as a unifying principle in the aetiology of complex traits and diseases Petronis A., Nature (2010) 465(7299):721-7 doi: 10.1038/nature09230
- Epigenetics and the environmental regulation of the genome and its function Zhang T. and Meaney M., Annu Rev Psychol (2010) 61:439-66 doi: 10.1146/annurev.psych.60.110707.163625
Epigenomic Data: Visualize, Browse, and Download