Your science teacher asks you, “Do you want to pursue a career in science?” 

You answer, “I want to be a genetics researcher.” 

Your friend, Johny, answers, “I want to. Be a genetics researcher.” 

The words in both sentences are exactly the same: the only difference is the use of an extra period in Johny’s sentences (which has an impact on the overall meaning). However, your answer makes more sense; Johny says he wants to do something in science, but he’s also telling your teacher to be a genetics researcher – which doesn’t fit the context. 

This post wasn’t meant to give you an English lesson on the importance of intentional punctuation. Rather, this scenario is comparable to the mechanism of epigenetics – which I like to call the “punctuation of DNA.”

Essentially, the purpose of DNA is to code for a protein, which represents the “meaning” of the sequence of DNA bases shown above. Though not pictured above, a gene (region of DNA coding a specific protein) has to be “transcribed” into messenger RNA (mRNA), which in turn provides the instructions for producing the necessary protein. 

Epigenetics primarily comes to play in the process of transcription, as it helps determine which genes are expressed (or transcribed).

As seen above, there are epigenetic “tags” which bind to DNA, preventing transcription of certain proteins from occurring. The actual DNA code doesn’t change; but, different regions of it are being expressed, leading to a different “meaning” (in this case, there’s no protein). 

Of course, it’s more complicated than adding periods and commas to sentences; there are different epigenetic mechanisms, which will be discussed below.  

In order for genes to be transcribed (or expressed) RNA polymerase (the enzyme which is responsible for creating a single-stranded copy of DNA), must be able to bind to the promoter – a region of DNA upstream of the gene itself. 

Within the promoter, a CpG island exists – this is just a fancy way of saying that there’s cytosine-guanine base pairing in that region. 

Thus, DNA methylation occurs when a methyl group (CH3)  is added to the individual cytosine base, with the enzyme DNA methyltransferase (DNMT). As a result, the CpG island becomes methylated, and transcription is blocked. 

Humans have A LOT of DNA, and all of it must fit into the nucleus of the cell. In the nucleus, DNA exists chromatin – a stringy form of DNA (however, during cell division, this chromatin is condensed into chromosomes). Chromatin is formed with the help of histones: positively charged proteins that associate with the negatively charged DNA double-helix. 

Creating chromatin is like placing beads through a string. The first step is the formation of a nucleosome, which can be thought of as a “bead.” This is formed when eight histone proteins are wrapped with approximately two turns of the DNA double helix. Histones act like a spool, wrapping DNA around them like a thread. Gene expression can be regulated with how tightly these beads are wrapped. DNA that is tightly packed is called heterochromatin. Less transcription occurs here since there is no room for RNA polymerase to bind to the promoter and transcribe DNA; genes in this region are not expressed, and are considered to be silenced. On the other hand, euchromatin is not tightly wrapped, and there’s more room for gene expression. Euchromatin can become heterochromatin, leading to the silencing of certain genes; this is often true during the cell cycle, when the transcription of different genes is needed at certain points in the cell cycle. 

Furthermore, histones can be modified, impacting the expression of genes. Adding a methyl group to a histone protein causes chromatin to become more tightly wrapped, leaving less room for transcription. Meanwhile, acetylation – the removal of a positive charge from a histone – decreases the interaction between histones and DNA, leaving more space for transcription. 

The types of epigenetic modifications and their impacts are still being studied. While this post gave an overview of two major mechanisms, there are more. For instance, noncoding RNAs – or ribonucleic acid that doesn’t code for a protein – has the power to interact with DNA, thus influencing gene expression. MicroRNAs (miRNAs) limit gene expression by binding to the untranslated region of mRNA. Short noncoding RNAs (which are only twenty to twenty five nucleotide bases long) bind to specific complementary DNA sequences, silencing gene expression. Lastly, long noncoding RNAs can increase gene expression by recruiting transcription factors. 

We know that genes are inherited. But, what about the epigenetic tags discussed previously, such as DNA methylation and histone modification? This is an area that is still being explored. Currently, scientists know that a few hours after fertilization, ten eleven translocation (TET) proteins remove methyl groups from DNA coming from maternal and paternal genomes during a process known as zygotic genome activation, providing a “clean slate.” 

However, not all the marks may be removed, leading to a phenomenon known as epigenetic inheritance. According to an analysis of one of three successive generations in Sweden, one generation’s nutritional status during its years before puberty correlated with the longevity of and morbidity experienced by that generation’s grandchildren; this demonstrates how the environment has a complex interaction with the epigenome.  

We’ve only known about the existence of the epigenome for a short period of time. Nonetheless, epigenetics has many implications in our overall health. It is key to regulating gene expression across different types of cells. For example, red blood cells express the gene HBB to produce hemoglobin protein, enabling oxygen transport. The DNA within all cells is the same, which means that the HBB gene is present in the genome of every other cell type in the body. Under normal conditions, permanent DNA methylation of the promoter of this gene leads to lifelong restriction of transcription in other types of cells (i.e. neurons). This allows for regulation of gene expression and differentiation of cells. 

Furthermore, in mice, a lack of methylation can lead to the expression of the agouti gene, which leads to a yellow coloration of the mice and predisposes them to obesity and diabetes as adults. Often, this is a result of mother mice consuming an unhealthy diet, specifically one that lacks folic acid – a crucial methyl-donating substance. 

Epigenetics has even been implicated in the formation of cancer. Hypermethylation of the CpG promoter region in tumor suppressor genes increases the likelihood of cancer, and is due to a potential imbalance between DNA Methyltransferase. The cancer genome can also undergo hypomethylation across the entire genome, leading to the overexpression of certain proto-oncogenes. In addition, the overexpression of certain DNA methyltransferases (ie DNMT1, DNMT3a) has been observed in multiple cancers, including colorectal, hepatocellular, pancreatic, and others. In fact, current areas of cancer research are focusing on using methylation patterns to detect cancer, and using drugs to affect these methylation patterns in the cancer genome without affecting the transcription of other key genes. 

It takes more than words to form a proper sentence (hopefully you took more than that away)! In all seriousness, epigenetics is an emerging field – one scientists are still trying to understand. There are many mechanisms that influence gene expression (which in turn allows the body to function properly), and unraveling them could be key to finding cures to numerous diseases and genetic conditions. 

Now, maybe you can tell your science teacher that you would like to be an “epigenetics researcher” – with the correct punctuation of course. 

Explore these references to dive deeper into the concepts discussed in this article, as well as to catch a glimpse of current epigenetics research! 🙂

Daxinger, Lucia, and Emma Whitelaw. “Transgenerational Epigenetic Inheritance: More Questions Than Answers.” Genome Research, vol. 20, no. 12, Nov. 2010, pp. 1623–28. https://doi.org/10.1101/gr.106138.110. 

“Epigenetic Inheritance and the Moral Responsibilities of Mothers.” AMA Journal of Ethics, vol. 15, no. 9, Sept. 2013, pp. 767–70. https://doi.org/10.1001/virtualmentor.2013.15.9.stas1-1309. 

Fessele, Kristen L., and Fay Wright. “Primer in Genetics and Genomics, Article 6: Basics of Epigenetic Control.” Biological Research for Nursing, vol. 20, no. 1, Nov. 2017, pp. 103–10. https://doi.org/10.1177/1099800417742967. 

Garvan Institute of Medical Research. “DNA Methylation and Cancer – Garvan Institute.” YouTube, 12 Nov. 2015, www.youtube.com/watch?v=W-S84J4zK9E. 

MacDonald, William. “Epigenetic Mechanisms of Genomic Imprinting: Common Themes in the Regulation of Imprinted Regions in Mammals, Plants, and Insects.” Genetics Research International, vol. 2012, Feb. 2012, pp. 1–17. https://doi.org/10.1155/2012/585024. 

News-Medical. “Chromatin Types and Functions.” News-Medical, 30 Aug. 2018, www.news-medical.net/life-sciences/Chromatin-Types-and-Functions.aspx#:~:text=Euchromatin%20can%20be%20transitioned%20into,such%20as%20during%20an%20infection. 

Obesity, Epigenetics, and Gene Regulation | Learn Science at Scitable. www.nature.com/scitable/topicpage/obesity-epigenetics-and-gene-regulation-927. 

Wu, Hao, and Yi Zhang. “Reversing DNA Methylation: Mechanisms, Genomics, and Biological Functions.” Cell, vol. 156, no. 1–2, Jan. 2014, pp. 45–68. https://doi.org/10.1016/j.cell.2013.12.019. 

Yuan, Cheng, et al. “Targeting Epigenetic Regulators for Cancer Therapy: Mechanisms and Advances in Clinical Trials.” Signal Transduction and Targeted Therapy, vol. 4, no. 1, Dec. 2019, https://doi.org/10.1038/s41392-019-0095-0.