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Pulling out gene silencers

Only in cells with Nef (left) does Eed stay outside the nucleus (right). Baur/Elsevier

Heterochromatin's repressive hold on DNA transcription can only be relinquished when activators enter the nucleus. Or so the theory goes. But now Vanessa Witte, Andreas Baur (University of Erlangen, Germany), and colleagues find that a heterochromatin component can be pulled from the nucleus by both the HIV protein Nef and activated integrins.

"This is a really new concept—that chromatin-associated proteins are shuttling," says Baur. The shuttling Eed protein, a polycomb group (PcG) heterochromatin factor, is captured at the plasma membrane by either membrane-associated Nef or activated integrins.

Eed first came to the attention of the German group as a Nef-binding protein. Injection of Nef into cells led to translocation of Eed out of nuclei to the cytoplasm. This reduces or eliminates the association of Eed with the integrated HIV DNA and increases HIV transcription. During an infection, these effects may be mediated by the small amount of Nef that the virus brings in with it.

The interaction between Eed and integrins has been noted before, but Witte et al. are the first to demonstrate that Eed shuttles out of the nucleus and binds to the plasma membrane after integrin activation, thus increasing HIV transcription.

The capture of Eed at signaling complexes may, Baur suggests, ensure that the nucleus is derepressed even before it receives activating signals from the plasma membrane. Other signaling complexes may use the same dual strategy.

Reference:

Witte, V., et al. 2004. Mol. Cell. 13:179–190.[CrossRef][Medline]

William A. Wells

wellsw{at}rockefeller.edu

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This Article Full Text (PDF, 702K) PPT slides of all figures Alert me when this article is cited Services Email this article Similar articles in this journal Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Wells, W. A. Search for Related Content PubMed Articles by Wells, W. A. Social Bookmarking                            What's this?