What are epigenetics?

What is epigenetics? So while we've been really focused for the last 10 to 20 years on the DNA mutations and cytogenetic abnormalities in leukemia, we're finding that a lot of the genes that are responsible for the outgrowth of leukemic cells are genes that are responsible for what we call epigenetics. That's how does a cell turn on and turn off the right genes in a way that is heritable to its daughter cell when it divides. So essentially there are two different categories of epigenetic modifications to the DNA inside a cell that we've been studying and trying to better understand. One is called DNA methylation. So a carbon group gets put onto one of the nucleotides called cytosine, the Cs in the DNA, and that changes what can bind to it, the shape of the DNA, and the function of the DNA. Those methyl groups are ubiquitous throughout the entire genome. In a normal function, those methyl groups get added or removed as a cell will change its type and will help instruct what parts of the genome should be turned on to be transcribed into RNA and then made into protein and what parts should be silenced. The other main category of epigenetics is something called histone modification. So in every cell of our body there's six feet of DNA in a teeny, teeny, tiny little nucleus. And so it has to be organized. And one of the ways it's organized inside a nucleus is to wrap the DNA around these protein structures that look sort of like an eight marble square and wrap it around the DNA. With the ability to either be opened and moved or wrapped in a semi-permanent or permanent manner to essentially repress that DNA from ever being turned on again. And so those eight marble spheres that the DNA is wrapped around have a tail that can get modified with different types of biochemical modifications. Methylation, acetylation, ubiquitination, all of these are chemical processes that instruct the histone itself to really inform how open, closed, or plastic that region of the DNA can be. And so broadly we categorize this into two different types of what we call chromatin. Chromatin is the DNA and the histone kind of bound together. Some are open and accessible and able to be turned on. We call that Euchromatin. And some are really condensed and repressed. And we call that heterochromatin. There's other proteins that will bind to it that are able to kind of modulate this process. It turns out a lot of the genes that are responsible for modulating this process are in fact mutated in not only leukemia but lots of different types of cancers. So this is a huge frontier for how not only normal cell physiology functions, but it's a major place where we'll, with better knowledge and better tools, be able to intervene in lots of different types of cancers. So let's say you've got a new appliance in your house. And that new appliance comes with an owner's manual. That owner's manual may have lots of different models of your appliance. But you only want to read the part that's important to you, to your appliance. And so the areas in a different language that you don't understand or for a different model are parts of that instruction manual that are not important to you. So those are silenced. It's not that they're ripped out and thrown away. They're still in the instruction manual. But they're not important to you. So that's what epigenetic silencing in a cell is responsible for. It's making sure that the part that you need is open and accessible and ready to be read and turned into the right genes and proteins that you need in order to function as a cell. But the stuff you don't need has to be silenced. Otherwise you might accidentally start installing or following the directions for a different type of model of appliance and do the wrong thing. And that would be bad. And so that's really how these DNA methyl groups, how these histone modifications are informing a cell to know where should we look for instructions, what should we turn on, and what should we totally disregard because it's not important to the type of cell that I am right now. The whole genome is an old encyclopedia in print. It's enormous in its tone. You can't read the whole thing, nor do you want to read the whole thing. You want to go just where you need for the question that you have, for the application that you need. For red blood cells, that means turning on hemoglobin. That means turning on iron metabolism proteins. For a white blood cell, that means turning on the right things that will help you clear an infection, something like called myeloperoxidase, something called perforin. You need to turn on those genes and express those genes. Otherwise, you can't be a white blood cell or a red blood cell. You can't be a red blood cell if you don't have hemoglobin, right? So a neuron needs dopamine and neurotransmitters. You don't want to be turning those things on in a red blood cell. And so there are some genes that most cells use, like cytokeratin structural molecules, but there's lots of genes that are just specific to that type of cell. Every cell has the same DNA, the same six-feet of DNA. And so it's really important that a cell doesn't have to read through the entire six-foot genome, that it has these physical markers to know where it needs to look.