Chromosome Organization within the Nucleus
5
It is likely that loci targeted to the
NE will fnd themselves in a highly spe-
cifc subenvironment within the nucleus,
which might have properties diFFerent
From those in the nuclear interior. Cer-
tainly, such loci would have the oppor-
tunity to interact with many proteins oF
the NE that would be eFFectively invisi-
ble to loci that were Found in the nuclear
interior. Direct interactions with NE pro-
teins are indeed thought to play a role in
gene silencing, as discussed below. How-
ever, in addition to a direct eFFect on the
NE-targeted loci, the attachment oF chro-
mosomes to the NE Forces the rest oF
the chromosome into a nonrandom ra-
dial positioning, in which even loci not
actually attached to the NE will tend to
occupy specifc radial distances relative to
the surFace. This nonrandom radial posi-
tioning has been systematically explored
in
Drosophila
, but has also been seen in
mammalian cells. This nonrandom radial
position is likely to have signifcant eFFects
on chromosome interactions (see Sect. 6
below).
2.4
Retention of Mitotic Chromosome
Geometry
During anaphase, chromosomes become
aligned such that all centromeres cluster
together as they move to the pole, while
the telomeres trail behind. When the
chromatin decondenses in telophase, this
arrangement should result in a polarized
nucleus in which telomeres are at one
side oF the nucleus and centromeres at
another. This is generally reFerred to as
the
Rabl Confguration
aFter its discoverer,
Carl Rabl. This Rabl confguration has
been clearly demonstrated using ±ISH
in a wide range oF cell types. The Rabl
orientation aFFects not just the position
oF centromeres and telomeres, but oF all
the chromatin in between. This has been
most clearly shown in
Drosophila
embryos,
in which loci spanning a chromosome
arm were shown to occupy a precise
position along the nuclear axis, in an
order that Follows precisely their linear
order along the chromosome. The Rabl
arrangement is most dramatic in cells
that
are
dividing
actively,
and
tends
to
become
less
obvious
in
cells
that
have
arrested
in
the
cell
cycle.
This
is
likely
to
reflect
the
slow
diFFusive
motion oF chromatin during interphase,
such
that
the
longer
a
cell
remains
arrested
Following
division,
the
more
the
mitotic
chromosome
arrangement
becomes distorted.
In addition to aligning during mito-
sis, chromosomes also become condensed
into spatially separated objects. When the
chromatin decondenses in telophase, this
spatial separation tends to Force the chro-
mosomes into
nonoverlapping regions
within the nucleus. Indeed, a variation
on ±ISH called chromosome painting,
in which entire chromosomes are vi-
sualized using a pool oF DNA probes,
has shown that interphase chromosomes
generally remain separated into nonover-
lapping ‘‘territories.’’
The combined eFFect oF specifc NE in-
teractions and the retention oF mitotic
arrangement is to set up a highly nonran-
dom arrangement oF chromosomes within
the nucleus, such that diFFerent loci tend to
occupy specifc subregions oF the nucleus.
Because this positioning is a by-product
oF large-scale chromosome arrangements,
there tends to be a lot oF variability in
the position oF individual loci, such that
the nonrandomness oF nuclear architec-
ture is best viewed as a statistical trend,
rather than as an absolute predetermined
arrangement.
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