Cell Nucleus Biogenesis, Structure and Function
411
the availability of heterochromatin pro-
teins. Ectopic genes in active chromatin
also behave unpredictably. For example, it
is possible to analyze gene expression from
arti±cial gene constructs introduced in pre-
determined target sites by homologous
recombination. However, even when the
chromosomal environment is controlled in
this way, some genes display unpredictable
patterns of ectopic expression, con±rming
that gene location at least has the potential
to influence expression.
The expressional status of a gene can
also be shown to influence its nuclear
location. Studies on the lymphoid lin-
eage of mammalian cells have shown
that the inactivation of gene expression
correlates with relocation of a gene to het-
erochromatic nuclear sites. During this
process, the sequence-speci±c transcrip-
tion factor Ikaros becomes associated both
with the silenced gene and with local
centromeric heterochromatin. Ikaros is
able to bind both a target promoter and
sites within the
α
-satellite repeats, so pro-
viding a means of driving appropriate
genes into inactive heterochromatic sites.
During B-lymphocyte development, the
immunoglobulin H (IgH) and IgK loci
are located at the nuclear periphery in
hematopoietic progenitors and pro-T cells
and in the nuclear interior in pro-B nuclei.
The inactive loci are associated with the
nuclear lamina and must move to active
sites within the nuclear interior before re-
combination and transcription of the IgH
and IgK loci can occur.
3.7
The Principles of Global Nuclear Structure
Thinking about the organization of major
nuclear compartments such as nucleoli,
the small nuclear bodies, sites of dedicated
nuclear function – within factories – and
chromosome territories leads us to assess
the general principles that underlie nu-
clear architecture.
3.7.1
Organizing the Cytoplasm
A worthwhile way of approaching this is-
sue is to ±rst appreciate how major cellular
activities are organized in the cytoplasm.
As we have already seen, mammalian cells
have a cytoplasmic compartment that is
highly structured, with many membrane-
boundorgane
l
les
.Bu
ti
tisv
i
ta
ltorecog
-
nize that this apparent structure belies the
extremely dynamic nature of the cytoplas-
mic compartment. It is well known that
membranes flow so that lipid bilayers can
readily fuse one with the other. The use of
GFP (green fluorescent protein), as a tool
to study the dynamic behavior of various
proteins of interest (each fused to GFP) in
living cells, emphasizes this point. The dy-
namic properties of mitochondria provide
an outstanding example: while an elec-
tron micrograph of a ±xed mammalian cell
might suggest that the cytoplasm contains
numerous distinct mitochondria, live-cell
studies show that these structures contin-
ually fuse with and bud from much larger
mitochondrial networks. The endoplasmic
reticulum, membranes of the Golgi ap-
paratus, and membrane vesicles that lie
downstream of the Golgi on the vesicle
export pathways, each perform functions
that require their components to be in a
continual state of flux. However, while the
observed intracellular activities might ap-
pear to be both dynamic and chaotic, they
are in fact highly structured. Membrane-
bound vesicles are too large to move inside
the cytoplasm by diffusion, and move in-
stead by energy-dependent processes that
are directed by cytoplasmic motor pro-
teins. The basic components needed to
achieve this are the motor protein com-
plexes themselves and a series of networks
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