1. How is the 2 meters' worth of DNA in every human cell (diploid) compacted to fit into a nucleus of less than 15 microns? Describe the various ways in which DNA is compacted, describing the proteins or structures involved at each level and the degree of compaction provided.

2. List the five major types of histone proteins, and describe what role each of them plays in the nucleosome. Based on what you know about them, which histone protein(s) do you think might be the most evolutionarily conserved? Which are likely to be the least conserved?

3. What are the “tails” of the histone proteins, and how are they distinguished from the rest of the protein?

4. Describe the interactions between the histones and DNA that determine the DNA's path around the histone octamer. How does the manner of DNA wrapping around the nucleosome alter DNA topology?

5. Compare the molecular interactions that occur between the histone proteins and DNA and those that occur between DNA and sequence-specific binding proteins such as transcription factors. How do the differences in binding mechanisms relate to the different roles of each of these types of proteins?

6. Once a nucleosome has formed on a particular stretch of DNA, an assembled nucleosome is relatively stable, but it is based on weak bonds and the association of a given stretch of DNA with the histone octamer is transient. The physical association between the histone octamer and DNA can be disrupted in numerous ways, including by spontaneous, random processes as well as by specific, active mechanisms.

The spontaneous processes simply reflect the weak nature of the bonds holding the histones and the DNA together: because weak bonds are inherently transient, histones will release parts of the bound DNA at some frequency. Describe why is it important that nucleosomes can be destabilized?

7. You are characterizing a transcriptional repressor in your favorite organism, and you perform a co-purification experiment to identify proteins that physically interact with the repressor. Using this approach, you identify an interacting protein that appears to have deacetylase activity. Speculate as to how this enzyme could be involved in transcriptional repression.