Did You Ever Wonder . . ?

Architecture in a cell nucleus
 
Together, DNA and histone proteins form nucleosomes, and nucleosome fibers fold into loops of chromatin.

To fit into the cell nucleus, DNA winds around proteins called histones like thread on a spool. The resulting bundles are called nucleosomes. Thousands of nucleosomes, linked by continuous DNA like beads on a string, coil into fibers, and the fibers fold into loops. The whole tangle of protein and DNA is called chromatin.

Tight coiling and folding complicate but also help regulate how genes work. For a gene to be read, the double-stranded DNA that encodes it has to be unzipped. Terumi Kohwi-Shigematsu's work over the past decade has concentrated on the details of how this happens.

She and her colleagues discovered that in certain kinds of cells -- especially the immune-system precursor cells called thymocytes -- a particular protein in the nucleus, SATB1, forms a cagelike network. The places where chromatin loops attach to this framework serve to divide it into distinct domains in which chromatin modification and structure are regulated. The domains contain groups of genes necessary for thymocyte development and functioning.

SATB1 does more: it provides a "landing platform" where special enzymes can go to work on the chromatin, rearranging it to access specific genes. Some of these enzymes modify histones; others move nucleosomes around. Histones have "tails" -- structures like little monkey tails that clasp DNA and grip other histones; chemical reactions make them grip or relax.

The sites where SATB1 binds to the DNA in chromatin loops are exactly those places where double-stranded DNA can readily unwind when subjected to negative strain -- like what happens when a rope is twisted in the opposite direction from the way its fibers are wound.

Thus SATB1 is both a structural element of the cell's nucleus and a crucial factor in the biochemical processes that regulate gene expression at different stages of a thymocyte's development into mature immune-system cells.

Additional information

More about SATB1

"Tissue-specific nuclear architecture and gene expession regulated by SATB1," by Shutao Cai, Hye-Jung Han, and Terumi Kohwi-Shigematsu, in Nature Genetics, May 2003 (requires subscription)

Did You Ever Wonder Web Site

Ernest Orlando Lawrence Berkeley National Laboratory