416
Cell Nucleus Biogenesis, Structure and Function
interchromatin space, inside each territory
and largely excluded from the domains
of chromatin. This approach and other
high-resolution studies support the view
that transcription centers are restricted
to the RNA-rich interchromatin compart-
ment. This interchromatin compartment
supports all the major chromatin func-
tions – and it is within this compartment
that any nuclear matrix must form.
4.1
Chromatin Structure and Function
While appreciating that the way nuclei are
organized might have a profound impact
on nuclear function, it is also important
to understand how DNA is organized in
order to provide an amenable template
that supports the major functions. In
this respect, it is necessary to understand
how DNA is packaged as chromatin and
how the properties of this DNA–protein
complex impact on function.
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known that different genes are expressed
to quite different extents and that many
are expressed in speciFc cells and at pre-
cise times during development. This begs
the question: how are different levels of
gene expression maintained? ±or a speciFc
gene, chromatin status and the availability
of activating transcription factors will com-
bine to establish an engaged transcription
complex that drives RNA synthesis. The
role of chromatin structure is clearly im-
plicit in the success of this process. It has
been know for many years that active and
inactive genes have quite distinct chro-
matin states and that inert chromatin is
able to spread – and so downregulate the
previously active genes. Two general fea-
tures are fundamental in protecting the
functional status of the active genes. The
Frst concerns the maintenance of a fluid
and active chromatin state through histone
modiFcation. The second requires that
genes are organized into chromatin do-
mains that behave as the functional units
of gene expression. The structure of these
domains, at least within the conFnes of
their natural chromosomal locus, might
ensure that genes are expressed at the de-
sired levels in appropriate tissues and at
the required times during development.
4.1.1
Chromatin Function
Work that determined the genetic code
that deFnes humanity represents a land-
mark of scientiFc endeavor. But with this
treasure comes the realization that it will
not always be possible to decode infor-
mation held within the genome in a way
that might allow us to predict patterns
and levels of gene expression in differ-
ent cell types and at different stages of
their development. Some aspects of gene
expression control are genetic in origin.
Most notably, we have seen how gene
expression is activated when transcrip-
tion factors interact with their cognate
recognition motifs in gene promoters and
other activating sequences – such as en-
hancers – to form a complex that recruits
the transcription machinery to a gene.
This process of sequence-dependent as-
sociation of speciFc proteins with deFned
sequence elements within DNA can be
studied in molecular detail, and is con-
ceptually simple to understand. In higher
eukaryotes, in particular, these genetic
controls are supplemented by a variety of
‘‘epigenetic’’ factors that modulate chro-
matin structure and both chromosome and
nuclear architecture.
4.1.2
DNA Packaging and Chromatin
Somatic mammalian cells are usually
diploid;
they
contain
two
sets
of
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