epigenetics & the histone code

The DNA in our bodies is very long - if I remember correctly, unfurled, the DNA in a single cell would be something like a meter or about three feet long. Somehow this manages to be packed into a cell about 1/100th (~20 microns) the diameter of a human hair (~200 microns).*

If you've ever tried to wind or unwind a ball of yarn, you can appreciate the difficulty of attempting to keep DNA in order. Now imagine needing to access, say, the middle of a mile-long piece of yarn at a moment's notice. You can pack it any way you want, but you have to fit in your suitcase, or at least get it small enough to lay on a bed. What kind of strategy would you use to both pack and be able to quickly access it? (Hint: winding it into a single gigantic ball is probably not the best way, nor is leaving it in a gigantic tangled heap.)

You may have thought of winding the yarn not just into one ball but into several, starting one, leaving a bit unwound, then winding another ball, all the way along the length of the yarn. Even better, wind it on a stick or something for a ways, leave a length of yarn, then start winding it around another stick. The sticks are like the "histones" in the body, which are proteins for winding DNA on. The yarn, of course, is analogous to DNA.

If you're really smart you could wind up all the yarn into lots of little packages on lots of little sticks, but leave the middle piece unwound so you could get to it quickly. If you knew you wanted to get to many different pieces you could leave those unwound, but wind up the parts you don't need.

This is very similar to how the body organizes and keeps track of DNA [Wikipedia graphic]. It winds it on histones, packs those histones together into bigger substructures, and on and on until you are at the level of the chromosome, or the big X"-like structures of compacted DNA that can be seen with a microscope.

If you thought about adding little tags to the yarn and various balls to remind you which to keep wound and which to unwind, it's a pretty good idea too. The cell puts various little tags on parts of the DNA to tell it whether it will be needed or not, and consequently, it packages it to be accessible or not.

The tags, in the case of the cell, are molecular: for example, acetyl or methyl groups on DNA that presumably act in different ways to allow (or not allow) cellular machinery to access the DNA for transcription into proteins. But what how exactly do they do that, and what does the code say? From that, can we predict what will or won't be transcribed for a given cell, just by looking at the histone code?

Not yet, for sure. There are only intriguing hints, but I suspect by the time I am ready to retire the amount of knowledge about the area will be astonishing.



*See a basic - almost corny - but effective animation of the spatial scales of biology at http://www.cellsalive.com/howbig.htm.