Bruna Mascaro, PhD
The lifestyle concept includes different factors such as diet, behavior, stress, physical activities, work and consumption habits, among others. The genetic background and environmental factors are directly related to lifestyle, and epigenetic processes have been increasingly related to these phenomena.
The word epigenetic is old, Aristotle already believed that all of our characteristics come from a process called “epigenesis”. Then, in the early 1940s, the biologist Conrad Waddington started to use the word epigenetics to refer to the way genes interact with the environment in the construction of organisms.
It is interesting to think that we originate from a fertilized egg, and as the embryonic development progresses, that egg divides into thousands of cells with the same original genetic information. However, for the proper construction of the organism, cells need to develop into different types, such as blood, neural, muscle, bone cells, etc. Therefore, it is necessary that there is a factor responsible for turning genes on and off properly, and then direct the differentiation of each cell type. This “non-genetic” factor is epigenetics.
After all, what is epigenetics?
Involving the study of an immense diversity of biological phenomena, epigenetics encompasses concepts of cell development and differentiation, metabolism, diseases, phenotypic variability, heritability, metabolism, among others. Epigenetics describes molecular events that occur in DNA, but do not affect the DNA sequence at all.
In fact, today it is known that genetic activity can be regulated like a light switch: it can be turned off or on at different levels. This regulation is carried out through chemical changes in the DNA sequence of our genes, without changing the identity of the base pairs that make up the DNA, acting literally on the genes, hence the term ‘epi’genetics. Epigenetic changes impact the way the DNA molecule is formatted, and consequently, regulate which genes will remain active, influencing an organism’s physiology and behavior.
It is not about the genes you have, but what your genes are doing!
Contrary to what many believe, the DNA that contains information about our genes is not capable of independent actions, which makes the regulation of these genes such an important mechanism for development as a whole. Genes are, in a way, induced to express themselves according to the environmental context (which is related to several factors, including other genes), making each gene behave in a unique way in each individual. This fact has already been proven in studies with identical monozygotic twins that originate from the same egg and, therefore, contain the same DNA sequence, however, their genes are expressed in different ways, which demonstrates that different experiences can leave “marks” on the DNA that affect the way genes are expressed.
Our DNA is capable of compacting at different levels, and since our DNA is highly compacted, mechanisms responsible for reading that DNA are not able to access it to interpret the information. When this happens, that highly compressed segment of DNA will be unable to be read, and then the proteins normally produced from that DNA fragment will not be processed.
An example of this are histones, which are large proteins associated with DNA and which assist in the compaction and decompression of DNA, which can be modified by various processes. These epigenetic DNA alteration processes, such as acetylation or methylation, makes the DNA more or less accessible for reading and processing (transcription). Acetylation of DNA makes it more accessible, leading to increased gene expression, while the addition of methyl groups – CH3 (methylation) makes the DNA segment more compact, leading to decreased expression of genes in that segment.
The environment is extremely capable of leading to epigenetic changes in DNA in extraordinary ways. A classic example is the study of queen and worker bees, which despite having identical genetic sequences, are completely different in terms of behavior, physiology and phenotype. In this case, the phrase “you are what you eat” represents exactly what is observed: Both queen and worker bees are initially fed with royal jelly, however, worker bees are quickly weaned and fed with nectar and pollen, while queen bees are fed with royal jelly throughout their development, maintaining this diet even in adult life. Recent studies have shown that royal jelly contains ingredients capable of inhibiting cytosine methylation in DNA, leading to increased expression of genes that are silenced in worker bees, which may explain the great phenotypic and behavioral difference between these two varieties.
In humans, the epigenetic phenomenon does not act as directly on the phenotype as observed in bees, however, researchers have increasingly demonstrated the impact of epigenetic changes on development, growth and disease.
Implications and studies on epigenetics
Epigenetic events are happening in our body at all times. For example, physical activity, what we eat or drink, can change the epigenetic pattern of our cells. From the understanding of how the expression of our genes is controlled, it is possible to imagine how genetic and epigenetic events collaborate to produce our characteristics.
Currently, epigenomics techniques have allowed researchers to investigate epigenetic changes throughout the genome, in a single experiment. This approach has been widely used, mainly, in the investigation of changes related to a large number of human diseases, such as cancer, autism and autoimmune diseases, among others. In addition, clinical researchers are in a constant search for the development of therapies with possible epigenetic targets.
The first human disease to be related to the epigenetic process was cancer, in 1983. Researchers found that tumor tissues from patients with colorectal cancer had a lower amount of methylated DNA than normal tissues from the same patient. Since methylated genes are typically turned off, loss of methylation can lead to increased gene expression. On the other hand, the increase in methylation can silence functions of important tumor suppressor genes.
This fine balance between “turning on and off” genes has been observed in several tumor processes, as well as during embryonic development. In this way, we are able to measure the importance of the epigenetic process for the precise and healthy functioning of organisms, and what impacts changes in this process can cause.
Understanding how the environmental context influences epigenetics, research related to post-transcriptional changes will have extremely far-reaching consequences. Epigenetic studies can be applied to different fields, and assist in several questions that remain unanswered. The knowledge that we have about the epigenetic process advances as new technologies become available, but it still lacks many future studies, and the more answers we have, new questions will arise. We are only facing the tip of the iceberg, of an entire network of interactions that involves this fundamental and intriguing process.
About the author:
Bruna Mascaro is a biologist specializing in molecular biology and Next-Generation Sequencing applied to oncology in clinical practice, with a Master’s and Doctorate from the Federal University of São Paulo. She is currently linked to the clinical laboratory of Hospital Israelita Albert Einstein.
 Waddington CH. The basic ideas of biology. Waddington CH. Towards a Theoretical Biology, Vol. 1: Prolegomena, 1–32. Edinburgh: Edinburgh University Press; 1968.
 Fraga, M. F. et al. Epigenetic differences arise during the lifetime of monozygotic twins. Proc. Natl Acad. Sci. 102, 10604–10609 (2005)
 Xu Jiang He, et al. Making a queen: an epigenetic analysis of the robustness of the honeybee (A pis mellifera ) queen developmental pathway. Molecular EcologyVolume 26, Issue 6. 2016
 Fazzari, M. J. & Greally, J. M. Epigenomics: beyond CpG islands. Nature Rev. Genet. 5, 446–455 (2004)
 Robertson, K. D. DNA methylation and human disease. Nature Rev. Genet. 6, 597–610 (2005)