420
Cell Nucleus Biogenesis, Structure and Function
obvious mechanism. The ATP-dependent
chromatin remodeling activities serve to
enhance the fluid properties of nucleo-
somes; in essence, they allow nucleosomes
to slide on DNA. The mechanism of this
process is not known in detail, but is
assumed to reduce the activation energy
needed to reposition a nucleosome core.
Hence, the chromatin remodeling ma-
chines provide a means by which nucleo-
somes can be repositioned to allow access
to previous inaccessible sites in DNA. This
activity will function cooperatively with the
histone modiFcation systems described
above to modulate and stabilize differ-
ent chromatin states. The combination
of these activities adds a huge complex-
ity to the epigenetic control of chromatin
function. Indeed, present estimates sug-
gest that something in the region of 50
chromatin-modifying complexes will col-
laborate to ensure that chromatin is an
extremely complex and structurally dy-
namic substrate.
4.2
Higher-order Chromatin Folding
The following section touches briefly on
chromatin architecture and in particular,
on differences in chromatin structure that
correlate with chromatin function, notably
RNA transcription. With this in mind, it is
worth emphasizing that only a very small
fraction – about 1% – of the DNA within
a mammalian cell is represented by mes-
senger RNA (mRNA) that is decoded to
generate proteins in the cytoplasm. About
10 to 20% of the DNA is in the euchromatin
that is transcribed to generate the primary
transcripts – called
heterogeneous RNA (hn-
RNA)
– that are subsequently processed to
form mature mRNAs. Individual cell types
have distinct expression proFles that are
determined by their developmental history
(differentiation program). About one-third
of the roughly 35 000 genes of human cells
are housekeeping genes that are expressed
inallcelltypes.Theothersareexpressedin
speciFc, specialized cell types and gener-
ally form facultative heterochromatin in
cells in which they are not expressed
and euchromatin in cells in which they
are expressed.
It is self-evident that DNA must be
highly folded so as to accommodate 2 m of
DNA in a nucleus measuring only 10
µ
m
in diameter (±ig. 10). The wrapping of
DNA around the nucleosome core begins
the condensation process that is contin-
ued by a hierarchy of higher-order DNA
folding. Nucleosomal chromatin can be
visualized by electron microscopy, as a
chromatin Fber of beads on a string; in
wh
i
che
a
chb
e
ado
rnu
c
l
eo
som
ei
ss
ep
-
arated from the next by a short stretch
of intervening linker DNA; in mammalian
cells these linkers are typically 50 to 100 bp
in length. As nucleosomes are 10 nm in
diameter, this is referred to as the 10-nm
chromatin Fber. Inside the cell, euchro-
matin is loosely folded as a locally chaotic
10-nm chromatin Fber. Interactions be-
tween different regions of the Fber might
generate local variations in chromatin den-
sity – though generally the chromatin will
appear diffuse. Heterochromatin, in con-
trast, is much more highly compacted.
Wh
ench
rom
a
t
ini
sv
i
su
a
l
iz
edinth
in
sections of mammalian cells a number of
folded forms can be identiFed. Aggregates
of the 10-nm Fber form a Fber with an
average diameter of
30 nm. Historically,
a chromatin Fber of this size has been
referred to as the chromatin solenoid – in
which six nucleosomes are held in one turn
of the solenoid by histone H1. Histone H1
is known as a linker histone; it is much
richer in heterochromatin, with about 1
copy per nucleosome core compared to
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