Revealed: How a master protein remodels chromosomes to orchestrate gene expression

A team led by Terumi Kohwi-Shigematsu of Lawrence Berkeley National Laboratory's Life Sciences Division has demonstrated that SATB1, a protein crucial to the development of the immune system, works by forming a network in the cell nucleus, attaching chromatin to the network structure at specific sites, and orchestrating remodeling of the chromatin over long distances to regulate gene expression.

"SATB1 determines when and how the genes are read -- when they are activated and when they are repressed," says Kohwi-Shigematsu. "We have shown that SATB1 regulates gene transcription by functioning as a 'landing platform' for several chromatin remodeling enzymes, which operate within large but well defined domains."

In the 10 October 2002 issue of Nature, the researchers report that, in thymocytes, SATB1 regulates the interleukin-2 receptor-alpha gene, IL?2Ra, by bringing specific chromatin and nucleosome remodeling enzymes directly to the gene site, and by directing nucleosome positioning over 7,000 base-pairs away.

Chromatin is the complex of DNA and proteins in the nucleus of the cell. It consists of DNA wound like thread around groups of histone proteins to form bead-like nucleosomes; this string of nucleosomes is coiled into fibers 30 nanometers (billionths of a meter) thick, and the fibers are folded into chromatin loops, further compacting the DNA. Thus a eukaryotic cell can pack the entire genome of the organism, well over a meter of DNA, into a nucleus only a few millionths of a meter across.

Many orders of chromatin folding are necessary to fit the genome into a small nucleus, and this complicates the process of gene expression. For a gene to be transcribed, the double-stranded DNA that encodes it has to be unzipped -- hard to do inside tightly wound chromatin. So gene expression depends on molecular machines that rearrange the chromatin, repositioning nucleosomes along the DNA fibers.

A decade ago Kohwi-Shigematsu a

Contact: Paul Preuss
DOE/Lawrence Berkeley National Laboratory

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