- The blueprint for the human body is encoded in genes, many of which hold the information necessary for the building of one or more proteins.
- Gene expression is the process by which information stored in genes is converted into proteins, the workhorse molecules that make up the body’s structures and carry its signals.
- Human genetic material includes about 3 billion bases, the “letters” that make up the DNA code containing genetic instructions.
The explanation was that we put the same genes to many uses with the help of complex regulatory mechanisms that govern when, where and to what degree our genetic material is accessed and activated. Some of these functions are performed by myriad non-gene DNA snippets called regulatory elements.
Still other recently discovered mechanisms contribute further to our genetic regulatory finesse, and without changing the instructions encoded in the DNA we get from our parents. Such changes represent the province of the emerging field of epigenetics and the focus of a recent UAB Epigenetics Symposium. The Mix – the UAB research blog – interviewed some of the presenters and is featuring the talks in a series.
Our guest for this podcast is Bruce Korf, M.D., Ph.D., chair of the UAB Department of Genetics, one of the organizers of the symposium.
Show notes from the Podcast:
:40 Epigenetics is defined as changes in human gene expression caused, not by changes in the order of base pair "letters" making up the DNA code (such changes are called mutations), but instead by chemical actions that affect the ability of the instructions encoded in a given stretch of DNA to be read and followed.
1:15 Researchers have long known that changes that turn genes on or off play a critical role in fetal development and in the response of humans to their environment, but not what controls those changes. It's now becoming clear that epigenetic mechanisms can permanently silence a gene, for instance, in a particular cell type.
2:01 Cells divide and multiply as the human fetus develops. Epigenetic changes do not just turn off a gene at a particular point in time, they turn it off in that cell and in all its descendants. That makes such changes useful a gene needs to be turned off permanently to, not only enable a stem cell to become a brain cell, but also to make it the proper sire of a line of many brain cells. The same genes that got a cell to the right stage in development may need to shut down for it remain the right cell type.
2:18 Methylation, the chemical attachment at a certain point on the DNA chain of a methyl group (one carbon atom bonded to three hydrogen atoms), is a principle type of epigenetic regulatory change.
2:25 Methylation is the attachment of a methyl group to cytosine, one of the four bases that encode genetic instructions with the DNA chain. When the methylation occurs at a cytosine that falls next to a guanine, another of the four bases, the methylation will make it possible for other proteins to bind to the DNA chain such that the surrounding gene is silenced.
2:47 The methylation interferes with a process by which DNA forms a complex with proteins called histones to form chromatin, which in turn makes stretches of DNA available to the gene expression machinery upon receipt of the right signals.
4:11 While we inherit our DNA code from our parents, epigenetic changes are not passed on. When a sperm or egg cell is produced, all the epigenetic marks are wiped clean. Thus, epigenetic fine-tuning of gene expression begins a anew with each person. Combine this with the fact that sunlight, cigarette smoke and the foods we eat make epigenetic changes, and we all become authors of our own gene code.
4:56 "Superfoods" like broccoli have linked to methylation status, and experiments months in mice have shown that diet can change the methylation status of specific genes (say those involved in cancer risk).
5:19 An interesting area of research in epigenetics is looking at lifelong risk of certain diseases (like Type 2 diabetes) based on events and influences that occur while that person is still in the womb.
6:18 Dr. Korf said the UAB epigenetics symposium is being held now because recent meetings on the UAB School of Medicine strategic plan revealed that many researchers were working in this area independently, and would benefit from collaborations.
7:35 Among the examples of key epigenetics research efforts underway at UAB, David Sweatt is looking at at the potential role of epigenetic changes in learning and memory, TrygveTollefsboll at fundamental aspects of epigenetic biology and Molly Bray at the impact of epigenetic changes on lifelong obesity risk.
8:00 The field is in its infancy in terms of determining epigenetic changes and what drives them tissue by tissue in conjunction with environmental factors. What is truly exciting now is the emergence of extremely powerful tools, the bioinformatics and high-speed genetic analysis technologies, that are driving the field forward. There will probably prove to be as many epigenomes as there are tissue types in the body.
9:14 Some of the most exciting near future advances are coming in the epigenetics of cancer. Mounting evidence suggests that some of the changes that turn genes off contribute to the development of cancers.
Tracking epigenetic changes may have predictive value in looking will benefit from a therapy and who is at risk for a cancer.
9:33 It has now been shown that some drugs interact with epigenetic changes, which raises the possibility of using drugs to turn back on genes silenced by abnormal, epigenetic mechanisms as part of disease.