Molecular Biology

The Bounds of Silence

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Science  14 Jun 2002:
Vol. 296, Issue 5575, pp. 1931
DOI: 10.1126/science.296.5575.1931a

Recent advances in visualizing intranuclear structure have revealed that the positions of chromosomal regions correlate with their transcriptional activity. That is, heterochromatic regions that are relatively inactive (or silenced) reside near the inside face of the nuclear membrane, whereas actively transcribing chromatin is generally found closer to the nuclear core. A striking confirmation of this architectural principle has been provided by Tanabe et al., who show that the nuclear localization of gene-poor and gene-dense regions, currently found in human chromosomes 18 and 19, respectively, has been conserved across humans and higher primates despite large-scale chromosomal rearrangements during evolution.

Ishii et al. now demonstrate that the interaction of boundary elements (which flank genes) with components of the nuclear pore complex (NPC) stimulates transcription of the bounded gene, counteracting the global silencing effect of heterochromatin. This interaction can occur either indirectly through the exportin protein Cse1 (and also through other members of the transportin family) or directly at the NPC basket via the Nup2 protein (but not via two other basket-associated proteins, Mlp1 and Mlp2). How the localization of these chromosomal regions might affect gene expression is not yet clear; the authors suggest that visiting the NPC neighborhood exposes a genomic domain to activating factors, such as histone acetyltransferases, and also facilitates the funneling of cytoplasmic signals to their genetic targets. — GJC

Proc. Natl. Acad. Sci. U.S.A. 99, 4424 (2002); Cell109, 551 (2002).

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