Cell Nucleus Biogenesis, Structure and Function
believed to reflect the transcriptional status
of highly expressed gene-rich chromoso-
mal regions. However, it remains to be
established if the chromatin movement
involved in the dynamic behavior of this
type of chromatin loop reflects any func-
tional association of speciFc genes with
remote active centers – that is, specialized
nuclear sites – which lie outside the terri-
torial boundary.
The molecular interactions that deFne
chromosome shape are not yet clear.
Many lines of evidence suggest that an
appropriate model to describe chromo-
some structure can be built around the
random spatial distribution of DNA foci
that contain roughly 1 Mb DNA (±ig. 7).
Interestingly, structures of this size cor-
relate with the replication foci, which, in
early S-phase at least, correspond with local
replicon clusters that are labeled together
at speciFc times of the replication pro-
gram. Even at the basic structural level
this implies that structure and function
must be related. How might this type of
arrangement impact on chromatin func-
tion? In mammalian cells, it appears that
the bulk of chromatin is only dynamic
over short distances – perhaps
or less. Beyond this, chromatin dynam-
ics appear to be constrained by chromatin
structure and numerous interactions that
serve to tether chromatin to a variety
of nuclear sites. Interestingly, in yeast,
chromatin is so dynamic locally that a lo-
cus might move by as much as 0
during a period of only 10 s. Remark-
ably, this allows a single locus to pass
through at least half of the nuclear vol-
ume in only 10 min. Such movements
are known to be energy dependent, im-
plying that they are probably related to
nuclear activities such as replication or
Chromosome Structure
some form of order within chromosome
territories and this is likely to influ-
ence function. It is generally assumed
that the familiar rodlike appearance of
metaphase chromosomes relies on the
properties of a proteinaceous axis or core.
It has been proposed that proteins within
such a core might bind DNA to gener-
ate a chromosome with arrays of DNA
loops of roughly 100 kbp. Simple staining
techniques, using silver-based histological
procedure, provide the most compelling
evidence for an axial core structure, yet
remarkably the proteins that might consti-
tute this structure
in vivo
are not known.
Isolated metaphase chromosome scaffolds
have two predominant proteins – ScI and
ScII – which for many years were the best
candidates for the core. These are now
known to be DNA topoisomerase II
SMC (structural maintenance of chromo-
somes) proteins. These proteins influence
DNA topology and mitotic chromosome
condensation and are essential for mito-
sis. However, studies on the behavior of
these proteins in living cells do not sup-
port the idea that either topoisomerase or
SMC proteins form a scaffold that orga-
nizes chromosome structure throughout
the cell cycle. The likely explanation for this
is that the observed structure reflects the
complex biophysical properties of the nu-
clear components that remain associated
with DNA throughout mitosis.
Functional Implications of
Chromosome Structure and Location
Gene expression from ectopic (i.e. un-
natural) chromosomal sites is extremely
unpredictable. Genes introduced into inert
chromosomal sites are generally inactive,
though expression can be modulated by
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