For Gene Activation, Location Matters
DOI: 10.1371/journal.pbio.0020381

Published September 28, 2004

Copyright: © 2004 Public Library of Science. This is an open-access article
distributed under the terms of the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any
medium, provided the original work is properly cited.

Citation: (2004) For Gene Activation, Location Matters. PLoS Biol 2(11):
e381.

Multicellular organisms contain a complete set of genes in nearly all of
their cells, each cell harboring the potential to make nearly any protein in
their genome. The same holds true for a single-celled bacterium or yeast.
Yet a cell activates only a fraction of its genes at any given time, calling
on a number of different mechanisms to activate the right genes at the right
time. To metabolize sugar, for example, a cell needs to synthesize proteins
involved in sugar metabolism, not protein repair, and vice versa. In a new
study, Jason Brickner and Peter Walter report a mechanism for gene
activation that depends on shuttling DNA to a particular location within the
nucleus.

In organisms whose cells have nuclei (eukaryotes), genomes lie within the
nucleus (called the nucleoplasm) but also interact with the inner nuclear
membrane. Transcription factors activate gene expression by binding to a
promoter sequence in the gene's DNA. The physical structure of DNA-which is
packaged with proteins into chromatin-affects gene expression by controlling
access to DNA. Where chromatin exists in the nucleus also influences gene
expression. Heterochromatin-stretches of highly condensed
chromatin-typically lines the nuclear periphery, and genes bundled into
heterochromatin are typically silent. Active transcription generally occurs
in the less condensed euchromatic regions. But since euchromatic regions are
also silenced when they associate with heterochromatin along the membrane,
it is thought that delivering chromatin to the nuclear periphery regulates
transcriptional repression. Brickner and Walter, however, found evidence of
the opposite effect-recruiting genes to the nuclear periphery can promote
their activation-suggesting that nuclear membrane recruitment plays a much
broader role than previously suspected in gene regulation.

To explore the consequences of chromatin location, the authors focused on a
yeast gene called INO1, which encodes inositol 1-phosphate synthase, an
enzyme involved in phospholipid (fat) biosynthesis. INO1 is also a target
gene of the "unfolded protein response," which is triggered when unfolded
proteins accumulate in the endoplasmic reticulum, a subcellular organelle
where secreted proteins are folded. The INO1 gene contains a regulatory
element (called UASINO) within its promoter region that responds to inositol
availability. Genes under the control of this element are transcriptionally
repressed by a repressor, Opi1, and activated by two transcription factors,
Ino2 and Ino4. The presence of unfolded proteins sets off a chain of events
to relieve Opi1 repression and allow activation of INO1.

Full Text at PLoS Biology
http://www.plosbiology.org/plosonline/?request=get-document&doi=10.1371/journal.pbio.0020381

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