Introducing Epigenetics: A Graphic Guide (Graphic Guides Book 0)

by Cath Ennis

“Epi-” means upon, or in addition; epigenetics is the study of how additional factors interact with genes to direct the processes that make our cells* and bodies work.

Our complete DNA sequence is called our genome*. All humans have extremely similar genomes, although we each have a slightly different version of the sequence. Almost every cell in your body contains its own copy of your unique version of the human genome.

The combination of DNA, histones and scaffold proteins, plus other proteins and RNAs that bind to the overall structure, is called chromatin*.

Normal cell differentiation is a one-way process that converts versatile stem cells into more specialized mature cells. This

John Gurdon (b. 1933) became the first scientist to artificially reverse cell differentiation. He took the nucleus of a fully differentiated tadpole gut cell and transferred it into a frog’s egg from which the nucleus had been removed. The cloned egg matured into a new, healthy frog. This experiment proved that fully differentiated cells retain all the genetic material needed to produce every cell in the body.

Transcription factors bind specific DNA sequences close to genes, and interact with the transcription machinery. The combination of proteins bound to any given gene helps to determine whether transcription takes place.

Like imprinting, X chromosome inactivation cannot be explained by transcription factors alone.

There’s more to us than just our genes: identical twins share the same DNA sequence, but have different personalities, preferences and medical histories.

2015, an international team headed by Peter Visscher and Danielle Posthuma published the results of 50 years’ worth of twin study data, concluding that, although the numbers vary between traits, the average breakdown is 49% nature, 51% nurture.

This research has identified non-genetic factors that increase our risk of developing a disease (like

However, working out how these factors interact with our genes has proven more difficult.

Most disputes about the definition of epigenetics concern whether the persistence of epigenetic landscapes during mitosis is an essential part of the description.

We now know that DNA and histone modifications represent additional layers of information superimposed onto the DNA sequence. Modern-day epigenetics is the study of this “information”

If the DNA sequence is an instruction manual that explains how to make a whole organism from a fertilized zygote, then epigenetic information is a highlighted and annotated version of the text.

Some molecular “colours” denote the parts of the text that need to be read most carefully, and others mark parts that can be ignored. The highlighting helps to determine which genes are transcribed and translated in which cells.

There are thousands of epigenetic highlighters, erasers and decoders, working together in a complex and carefully coordinated network.

DNA methylation causes gene silencing. Adrian Bird discovered decoder proteins in the cell nucleus that recognize and bind specifically to methylated C bases (mC). These proteins shut down transcription from genes that contain methylated DNA, preventing the production of the corresponding RNAs and proteins.

DNA methylation is the best-known example of a mitotically heritable epigenetic modification (see here). Even the strictest definitions of epigenetics include DNA methylation!

DNA methylation, histone modifications, chromatin remodelling and regulatory RNAs are involved in diverse processes throughout our lives, from the fertilized zygote’s first few cell divisions to the creation of offspring and onwards into old age. The discovery and study of individual epigenetic modifications represent small pieces in the much larger puzzle of how these processes work.

Epigenetics is already starting to help explain cell differentiation, imprinting, the interplay between nature and nurture, and some of the other gaps in our knowledge of genetics.

The cells that are reprogrammed twice are called primordial germ cells*, and will go on to produce the embryo’s own egg or sperm cells. The function of this second round of epigenetic reprogramming is to reset the epigenetic patterns of the next generation.

The discovery that environmental factors can cause epigenetic changes explains how our traits and susceptibility to disease are affected by both nature and nurture. The boundaries between these “opposites” are blurring.

Epigenetic modifiers range from the harmful – nicotine, benzene, arsenic, viral infections – to more benign molecules like folic acid and vitamin C.

One example of how childhood environments can have longterm epigenetic effects involves children who experience physical or emotional abuse, who often go on to suffer from lifelong poor health. Even people with no conscious memory of the abuse carry an increased risk of heart disease, cancer, substance abuse, depression and other conditions. Abuse causes permanent DNA methylation changes. The initial trigger is thought to be the stress response hormone cortisol, which abused children produce in large amounts.

The hope is that research in this field will help to identify pharmaceutical or other interventions that can help to protect child abuse victims from developing health problems later in life.

Exercise correlates with the silencing of genes that are involved in cell division and inflammation, which might help to explain the effects of exercise on cancer and other disease risks.

The discovery of epigenetic inheritance has raised an interesting question about evolution: if some of the epigenetic modifications that we acquire during our lifetimes can be passed on to our children and grandchildren, can they also affect how species evolve over many hundreds of generations?

The discovery of epigenetic inheritance in the late 1990s seemed to throw a lifeline to the older theory, however. Environmental exposures do sometimes seem to pass to later generations. Could there be room for a version of Lamarckism as one component of modern evolutionary theory, after all?

Epigenetic modifications might affect how individuals respond to environmental changes in the short term, but it seems very unlikely that long-term epigenetic inheritance can permanently change the characteristics of a species over hundreds and thousands of generations.