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The silence of the clones: new link between DNA replication and 'silent' chromosome architecture

Cold Spring Harbor, NY -- As genetically identical cells (such as those in an embryo) multiply, different sets of genes are switched on, and others off, giving rise to cells and tissues with distinctive properties (e.g. liver versus muscle). Such differential gene expression is determined in part by the large-scale architecture or chromatin structure of DNA. "Silent" regions of DNA are tightly packaged into forms of chromatin that are less accessible to transcriptional activators, the proteins that switch genes on. Active regions of DNA adopt alternate chromatin structures that are generally more accessible to transcriptional activators .

Now, Bruce Stillman and his colleagues at Cold Spring Harbor Laboratory have demonstrated how a set of proteins work in concert to duplicate both the basic sequence of DNA as well as silenced states of chromatin structure. The findings, published tomorrow in Nature, provide the first detailed mechanism to explain how both DNA sequences and their associated states of gene expression are coordinately passed on to future generations of cells.

In 1989, Stillman and his colleague Susan Smith (now at New York University Medical School) purified a human protein called chromatin assembly factor-1 (CAF-1). They showed that in a test tube, CAF-1 could wrap newly-synthesized DNA around chromosomal proteins called histones, forming "beads on a string." Such structures are the first level of higher order chromatin structure beyond naked DNA. "Beads on a string" (nucleosomes) can be wrapped into still higher orders of chromatin structure, ultimately yielding tightly compacted chromosomal domains that are transcriptionally silent.

Consistent with CAF-1's ability to assemble chromatin in cell free systems, Stillman and his colleagues subsequently found that CAF-1 is required for the inheritance of silenced domains of DNA in an intact organism (yeast). Both humans and yeast, and indeed all complex organisms, contain rel
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Contact: Peter W. Sherwood, Ph.D.
sherwood@cshl.org
516-367-6947
Cold Spring Harbor Laboratory
7-Nov-2000


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