Research of Histones

So we know what histones are and what they look like...what else is there?!

Chromatin Coiling and Condensing into a Chromosome

The fact that histones have been identified and can be diagrammed is great, but the really important research to be done is learning how histones function! Sure, we know that DNA wraps around histones, and that too many histones can overwhelm a cell, but what other functions do histones have? And, if we change these functions, what are the results?

Without research, we would not know much about histones at all. It's scientists like Dr. William "Bill" Marzluff and his friendly lab staff at the University of North Carolina at Chapel Hill that are exploring histones with new technologies in order to explain the ins and outs of histones.

Bill Marzluff

More specifically, Dr. Marzluff and his team look at how histone replication and the degradation of histone instructions are regulated. In other words, what controls when histones are present in the cell and how many are replicated.

If you would like to know more about Dr. Marzluff and his research at UNC, feel free to explore his lab website.

You may ask, "What importance does this research have?", or "How do histones affect me?"

Remember that histones are replicated during S phase--just like DNA--which means they are involved in the cell cycle. And in cancerous cells, the cell cycle is what gets messed up, resulting in over-active cell division and tumor growth. So, the general thinking in the Marzluff lab is that if we know how histones are regulated, maybe we can use that knowledge in cancer research and learn how to manipulate the cell cycle.

With the lab's research of histone regulation, Dr. Marzluff has discovered that without a signal from "command proteins", the instructions for making histones remain in the cell and histones continue to be produced. The command protein tells its "assistant", known as SLBP (Stem Loop Binding Protein) to get rid of the recipe for making histones so that histones will not continue to be produced.

Let's think about histone gene regulation as a story...

Mob Boss

Imagine the command proteins as a mob boss, who gives orders to other protein "workers" but never actually participates in the action. The command protein has these important documents (the instructions for making histones) that need to be shredded.

Shredded Documents

So, at the end of S phase, when no more histones are needed, the mob boss sends the signal to to shredder (SLBP) to "shred" the recipe for making histones. So when the mob boss sends the documents to the shredder, the instructions get destroyed so that no one knows how to make histones anymore. Therefore, histone production is turned off an no more histones can be made.

But, if something goes wrong, like a mutation and the mob boss never sends the documents to the shredder, the histones continue to get made because the instructions are still present in the cell.

Now, back to the cell:

When the mutation changes the function of the command proteins, and the signal for "instruction degradation" is not sent, histones continue to to be produced. And, like was mentioned on the Histone Properties page, with the histone mutant, too many histones are produced, preventing cells from dividing successfully, and causing the cell to become overwhelmed and die.

Check out what happens in fly embryos when they have the histone mutation!

You will see that as the nuclei try to divide, they often have trouble fully separating, resulting in "sticky" ends attaching to each of the nuclei. In one of the last cycles of division, you can see that some nuclei never successfully separate, resulting in nuclei that simply fuse back together after dividing.

We have seen that histones are proteins that are involved in the cell cycle. We have also explored a specific method for studying a protein--molecular cloning--and discussed some specifics of ACTUAL histone research. So how are histones and cancer related? How can we apply our knowledge of histones to cancer, itself?

Click the "Next" button to explore the relationship between histones and cancer!

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