The Molecular Perspective: Histone Deacetylase

STEM CELLS 2003;21:620-621 www.StemCells.com Our cells contain about 6 billion base pairs of DNA, which encode about 30,000 different proteins. As you might expect, however, we do not need all of this information at all times. At any given moment, each of the cells in your body is using somewhere between one-third and two-thirds of its DNA, and the rest is stored safely out of reach. DNA storage is the job of the histone proteins. In the nucleus, DNA is wound around histones to form nucleosomes, which further associate to form the condensed structure of chromatin. Nucleosomes are highly dynamic, and the information in chromatin can range from deep archival storage to an active lending library. The transitions between tightly protected chromatin to freely accessible DNA are controlled, in part, through modification of the histone proteins. Each histone contains a long, flexible tail that extends outward from the nucleosome. These tails are essential, but partially redundant: mutational studies in yeast have shown that cells can get by with only three or four of the eight tails in each nucleosome, but run into problems if all of them are removed. In cells, the tails are modified by adding acetyl groups, phosphates, methyl groups, adenosine diphosphate molecules, or even entire ubiquitin proteins. Together, these modifications form a code that determines the current state of the histone. By interacting with other nucleosomes and by interacting with a diverse collection of chromatin-remodeling proteins, these tails help to control the local structure of the chromatin. Acetylation is an important element in this histone-modification language. The histone tails contain many lysine amino acids, which interact favorably with the many negative charges on the DNA backbone. These tails are thought to wrap around the outside of the nucleosome, stabilizing the tightly coiled structure, and to extend to neighboring nucleosomes, interacting with the DNA and histone proteins there Fundamentals of Cancer Medicine Stem Cells®