Cell Nucleus Biogenesis, Structure and Function
415
that are believed to play important roles
in gene regulation. SATB1 in association
with MARs acts as a transcriptional re-
pressor to regulate gene expression during
T-cell development. This protein has the
classical properties of a nuclear matrix
component and deletion of SATB1 results
in defects in the temporal and spatial regu-
lation of many lymphocyte genes, leading
to an arrest of T-cell development. SATB1
is known to target chromatin remodel-
ing factors to speciFc chromatin domains
and so provide a mechanism for the
long-range regulation of gene expression.
SATB1 recruits histone deacetylase com-
plexes containing the NURD chromatin
remodeling complex to SATB1-bound sites
in the interleukin-2 receptor gene to elicit
speciFc deacetylation of histones within
the locus. In addition, SATB1 was shown
to target CHRAC and AC± chromatin
remodeling complexes to regulate nucle-
osome positioning over several kbp DNA.
SATB1 might also play a direct role in
recruiting RNA polymerase II to speciFc
nuclear sites.
3.7.4
Functions at the Matrix
Numerous experiments support the exis-
tence of a nuclear matrix that plays central
roles in nuclear function. An excellent ex-
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behavior of the runt-related transcription
factors (RUNX/CB±A/AML), which play
essential roles in cellular differentiation
and fetal development. A domain within
the RUNX transcriptional activators tar-
gets the protein to discrete subnuclear foci.
Removal of the targeting domain results
in lethal hematopoietic and skeletal phe-
notypes, and implies that for this class
of protein the correct nuclear location is
critical for the function. The behavior of
G±P-RUNX fusion proteins in living cells
conFrms that RUNX proteins occupy dis-
crete nuclear foci, the majority of which
are coincident with transcription sites and
associated with a low-salt nuclear matrix.
RUNX proteins also interact with Smads,
a family of signaling proteins that regu-
late various developmental and biological
processes in response to growth factors.
Interestingly, the RUNX proteins are re-
quired to target Smads to nuclear sites
where transcription is performed. This im-
plies that gene expression involves the
in
situ
integration of critical signals through
the assembly of regulatory complexes at
transcriptionally active subnuclear sites.
This work and other studies suggest that
activating factors engage appropriate nu-
clear sites that are competent to perform
gene expression and that the process of
transcription can only occur once a gene
has been recruited to the active center.
4
Integrating Nuclear Structure and Function
Having addressed different aspects of nu-
clear structure and function we should
now explore how these might be inte-
grated and assess if this process influences
our perceptions of nuclear organization.
The basic principles of chromosome ter-
ritory organization were outlined earlier.
However, it is important to remember
that these territories are not homogeneous
structures. It is possible, for example, to
use three-dimensional ±ISH techniques to
show that condensed chromatin as well as
the active chromatin compartment (using
speciFc antibodies for modiFed histones
found in transcribed chromatin) occupy
spatially distinct compartments from the
transcription factor T±IIH, RNA poly-
merase II, and hnRNP-U. Interestingly,
these proteins are present throughout the
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