6
Chromosome Organization within the Nucleus
3
Molecular Interactions That Specify Nuclear
Architecture
Nuclear architecture is maintained by
interactions with the NE and possibly
an internal nuclear matrix. Many stud-
ies over the past few decades have re-
vealed a number of candidate molecules
t
h
a
tm
i
g
h
ta
c
c
o
u
n
tf
o
rt
h
e
s
ei
n
t
e
r
a
c
-
tions. Such studies will really be the
key to understanding the function of
nuclear architecture, since in principle,
the identiFcation of the molecules in-
volved should allow the architecture to
be
perturbed
in
a
reproducible
way
and
the
effects
of
this
perturbation
tested.
3.1
Nuclear Lamins
What part of the NE is responsible for
binding chromatin? The nuclear lamins,
a family of intermediate Flament-like pro-
teins that form a network on the inner
surface of the NE, are able to bind speciFc
DNA sequences
in vitro
as well as his-
tones. Several lamin-associated proteins
can bind DNA or chromatin. It remains
unclear, however, whether these interac-
tions really occur in living cells. Moreover,
since lamins are thought to be involved
in reassembling the nucleus around chro-
mosomes during telophase, it is important
to distinguish between chromatin–lamin
interactions that are involved solely in
nuclear reassembly. A ±ISH analysis of nu-
clear organization during nuclear reassem-
bly in
Drosophila
embryos has shown that
the loci that interact with the NE during
in
t
e
rph
a
s
ea
r
eno
tth
es
am
ea
sth
elo
c
i
that interact with the NE during nuclear
reassembly.
3.2
Nuclear Pores
Nuclear
pore
complexes
(NPCs)
also
appear capable of interacting with chro-
matin. ±or example, one NPC protein
binds DNA
in vitro
. Moreover, the telom-
ere protein yKu70 can bind to the NPC
associated protein Mlp2, which is attached
to the NPC via an interaction with the
nucleoporin Nup145. All three of these
proteins are needed for telomeres to inter-
act with the NE. In electron microscopy
studies of the NE, the nuclear pores are
seen to extend long processes into the
nuclear interior, and these may be likely
candidates for the speciFc structures that
interact with chromatin. Because both the
nuclear lamins and the NPCs can associate
with chromatin, it is critical to distinguish
which set of molecules is required for a
given chromatin–NE interaction.
3.3
Nuclear Matrix
In addition to interactions with the NE,
chromatin might also interact with an in-
ternal structure within the nucleus called
the
nuclear matrix
. The nuclear matrix was
Frst deFned as the insoluble residue that
remains after isolated nuclei are heavily
extracted, and so its relevance to actual
structures
in vivo
has never been very clear.
A network of Fbers has been seen in nuclei
that might correspond to the matrix, but
only when using unusual resinless embed-
ding procedures for electron microscopy,
which raise concerns about potential arti-
facts. Two proteins in
Drosophila
,CP60and
CP190, appear to form a network within
nuclei of living
Drosophila
embryos, and
this network persists in the shape of the
nucleus even after the NE has broken down
and the chromosomes have congressed to
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