The last couple of months, we’ve talked a lot about the biopsychosocial model and how it explains some of the more complicated expressions of the brain. But biopsychosocial influences affect much more than just our brains. In fact, in the past few decades, there has been growing evidence that factors like environment and behavior can affect our bodies on a molecular level—through epigenetic markers. The term epigenetic refers to all of the molecular markers and modifications that change the way your DNA is read and interpreted. If DNA is the blueprint of life, then epigenetic markers are the labels and scale bars—completely necessary to build a structure that makes sense. While your genetic code will remain mostly stagnant throughout your life, epigenetic markers change in response to changes both inside and outside your body. And while not all of these changes get inherited, many of them do, extending the impact of environment and behavior to your children and your children’s children.
Pretty much every cell in your body has the exact same genetic sequence—which is why you can take a swab from your cheek and be reasonably certain that it represents the genetics of a cell in your heart or one from your left pinky toe. The 3.2 billion base pairs of DNA stored inside each of your cells are like a static barcode unique to you. The proteins in your cells use that barcode to figure out what sorts of molecules they need to make and in what ratios. But if every cell reads the barcode the same way, then what is the difference between a cell in the heart and a cell in the left pinky toe? And how come each of those cells has a different molecular makeup when you are a newborn infant versus when you are a 37-year-old adult? Unless you have been exposed to some highly mutagenic chemicals, the DNA in those cells won’t have changed much in that time. But babies are different than adults, and hearts are different than left pinky toes, so something else must be going on. Many of the programmed changes and cellular differentiations that dictate how each cell enacts its genetic barcode are controlled by epigenetic markers.
Epigenetic markers tag the DNA and its structural supports, altering the accessibility of certain genes and changing the molecular makeup of the cell as a consequence. The arrangement of these markers forms the cell’s epigenome, which adapts and responds to cellular and environmental cues. So the cells in your left pinky toe still have all the same genes as those in your heart, but epigenetic markers in the left pinky toe cells strategically switch off the genes that create cardiac-specific proteins (and any other unnecessary proteins). Epigenetic markers are essential for cell differentiation, defining what each cell needs to make and in what amounts to accomplish its cellular function, but these markers aren’t the same from person to person, and they can change over time. Not only do you have different DNA than someone else, but you also have a different epigenetic makeup. Epigenetic differences are part of the reason why identical twins aren’t completely identical as they grow older. Despite being genetically identical, twins can have different interests, personalities, and even disease risks. These differences arise from the different experiences and environmental exposures that each twin has, which influence them psychologically, socially, and biologically—through epigenetic markers.
The term epigenetics refers to a broad range of molecular markers and interactions that modify the expression of genes. One of the simplest epigenetic markers is the addition of a methyl group (a single carbon with three hydrogens) to the cytosine (C) DNA base. DNA methylation almost exclusively occurs on cytosine (C) bases that are directly followed by guanine (G) bases. These sites are called CpG sites—where the p refers to the phosphate group that connects subsequent DNA bases—clusters of CpG sites are called CpG islands. When a CpG island is heavily methylated near the start of a gene, that gene is effectively repressed. Methyl groups can be added to CpG sites by a group of enzymes called DNA methyltransferases (DNMTs), and they can be removed passively when the DNA is copied or actively by ten-eleven translocation (TET) enzymes. Hypermethylation of genes that should not be turned off—like tumor-suppressor genes—is a common cause of diseases like cancer. There is still a lot that scientists need to decode about the patterns of DNA methylation, how they change as we age, and how they’re inherited. But it’s becoming increasingly clear that DNA methylation plays a central role in adapting the static genetic code to environmental pressures.
DNA methylation works by physically blocking the binding site of the enzymes that copy DNA for translation into proteins. Another way this binding can be blocked is by wrapping the DNA tighter. In order to pack about 6 feet of DNA into each of your microscopic cells (you heard me right, 6 feet in each cell), the DNA has to be meticulously coiled and condensed using a group of scaffolding proteins called histones. DNA wraps about two times around a spool made from eight of these histone proteins to form a nucleosome. The nucleosomes coil up further to form a thicker fiber that loops around and condenses into a chromosome structure. The tightness of this coiling and condensing affects how accessible genes are for copying and translating. As such, the chemical modification of histones is a useful epigenetic marker for controlling gene expression. Unlike DNA methylation, methylation of a histone protein can either activate or repress a nearby gene, depending on the position of the methylation. The addition of an acetyl group (COCH3) to a histone loosens the wrapping of DNA around it, making it easier to copy. On the other hand, the removal of an acetyl group from the histone allows the DNA to wrap more tightly, condensing it and making it harder to access. Because they can inhibit genes important in tumor suppression, histone deacetylases (HDACs) are linked with several cancers, and HDAC inhibitors are often used as anti-cancer drugs.
DNA methylation and histone modification are really just the tips of the iceberg when it comes to epigenetics. There’s also a whole world of non-coding RNA molecules that mediate gene silencing. Together, all of these epigenetic markers and processes are partly responsible for the remarkable nuance and adaptability of biology. Even though scientists have almost entirely sequenced the human genome, they are only just beginning to pick apart the immense complexity of the epigenome.
Next week, we’ll talk more about epigenetic inheritance and how your actions may have consequences—for your grandchildren. For now, check out last month’s series on biological sex and gender. Comment on this post or email me at contact@anyonecanscience.com to let me know what you think about this week’s blog post and tell me what sorts of topics you want me to cover in the future. And subscribe below for weekly science posts sent straight to your email!
