Cell Nucleus Biogenesis, Structure and Function
413
proteins is by far the best-characterized
structural nuclear network. Roles played
at the nuclear periphery are particularly
clear. What remains more a matter of spec-
ulation is whether a diffuse lamin network
spreads throughout the nucleoplasm, and
if this could then support the nuclear func-
tions that many investigators believe take
place at a nuclear matrix.
3.7.2
The Nuclear Matrix – Fact or Fiction
This leads us to assess what the nuclear
matrix might be and analyze the functions
it might perform. We have seen that nuclei
can be plastic, so that they appear to have
a complex structure of nuclear compart-
ments, which generally represent centers
of nuclear function. These centers have
components that are inherently dynamic
and in general are not stable entities – this
is self-evident given that most are dis-
rupted during mitosis. However, while
these compartments might be plastic, it
is also interesting to note that the spatial
organization of sites such as transcrip-
tion and replication factories and nuclear
speckles is unaffected if nuclei are de-
pleted of chromatin (Fig. 8). This suggests
that the compartments are spatially con-
strained and raises the possibility that a
‘‘solid phase’’ exists within nuclei to pro-
vide a platform upon which the active sites
assemble. A ‘‘nucleoskeleton’’ has been
proposed to ful±l his role.
The nature of the nucleoskeleton and
related nuclear matrix remains a matter of
debate. Core ±laments that could provide
a form of continuity throughout the nuclei
have been described. These ±laments have
characteristic morphological features of
the intermediate ±laments seen through-
out the cytoplasm. The best-characterized
intermediate ±laments within nuclei are
undoubtedly the nuclear lamins. How-
ever, in addition to roles played by the
nuclear lamins at the nuclear periphery, re-
cent studies using GFP-lamin proteins and
classical high-resolution immunostaining
have suggested that a veil of lamin ±l-
aments spreads throughout the nucleus.
These observations support the idea that
a lamin-based network might pervade the
nucleoplasm to provide a framework to
coordinate the organization of various nu-
clear compartments. This idea, however,
remains controversial and it is still a mat-
ter of debate as to whether the lamins
might form a contiguous internal nucle-
oskeleton. As an alternative, the lamins
could feasibly play a structural role in the
short-range organization of nuclear com-
partments such as transcription centers.
3.7.3
Proteins of the Nuclear Matrix
The nuclear matrix is classically described
as an amorphous ±brogranular structure
that can be isolated from the nuclei by
hypertonic treatment following nuclease
digestion. By this de±nition the matrix
is perceived as being a product of the nu-
cleoskeleton/nuclear lamina networks and
associated proteins. The matrix typically
contains many hundreds of different pro-
teins, many of which have been studied
in detail. Two of the best character-
ized – SAF-A (scaffold attachment factor
A) and ARBP (attachment region bind-
ing protein) – were discovered because of
their association with the matrix attached
DNA elements. SAF-A turns out to be a
major RNA binding protein (hnRNP-U)
andARBPisapro
te
intha
tb
indsme
thy
-
lated DNA (MeCP2). SAF-A has been
shown to bind p300, a major transcrip-
tional coactivator, and so recruit active
genes to the nuclear matrix. ARBP, in
contrast, interacts with methylated DNA
in MAR elements and through an in-
termediary that contains Sin3A protein
recruits histone deacetylases to generate
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