410
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
0
.
5
µ
m
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
.
5
µ
m
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
transcription.
3.6.1
Chromosome Structure
Chromosome
structure
must
impose
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
α
and
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.
3.6.2
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
previous page 1084 Encyclopedia of Molecular Cell Biology and Molecular Medicine read online next page 1086 Encyclopedia of Molecular Cell Biology and Molecular Medicine read online Home Toggle text on/off