Chromosome Organization within the Nucleus
the metaphase plate. CP60 and CP190 are
components of the nuclear matrix deFned
biochemically, and thus may represent a
true matrix that exists as a coherent struc-
ture in living cells. This possibility deserves
more detailed investigation.
Interphase Chromatin Movement
The only way for chromosomes to be
held in a deFned arrangement is for their
mobility to be constricted. Otherwise, one
would expect the chromatin to diffuse
throughout the nucleus, like polymers in a
polymer melt, and rapidly randomize any
initially nonrandom conFguration.
Evidence for Chromatin Immobilization
Early cytological evidence suggested that
interphase chromosomes were fairly im-
mobile as judged by the similarity of
chromosome arrangements in successive
mitoses by the separation of parental
genomes in the Frst few divisions after
fertilization. Modern biophysical methods,
including photobleaching and
in vivo
mosome visualization, have conFrmed
the early impression that chromosome
movement is constricted during inter-
Evidence for Chromatin Diffusion
However, more detailed measurement of
interphase chromatin movement in living
cells, based on an application of submi-
cron single-particle tracking techniques to
individual loci tracked using a green flu-
orescent protein (G±P) tagging system,
revealed that interphase chromatin does
in fact undergo substantial and rapid dif-
fusion, but this diffusion is constrained
such that a given locus can only diffuse
within a small subregion of the nucleus.
In yeast and
, chromatin moved
with a diffusion constant of approximately
because of thermally driven
Brownian motion. But this diffusion was
conFned to a subregion with a radius of
roughly equal to 1to 5% of the nuclear vol-
ume. ±ollowing this Frst analysis of chro-
matin diffusion in yeast and
subsequent analyses have conFrmed the
result that interphase chromatin can dif-
fuse within a conFned region in a wide
range of cell types. More detailed analysis
has shown that the details of chromatin
diffusion depend on the timescale, and
that at very short timescales chromatin
movement is highly constrained, whereas
at longer timescales, chromatin is freer
to diffuse over larger distances. This sug-
gests that chromatin diffusion at short
timescales is constrained by interaction
with a structure (e.g. the nuclear lamina)
that itself undergoes slow random move-
ments. Nuclear pores have been shown
to turn over at a slow but detectable rate
such that if chromatin were constrained
by interactions with NPCs, then the slow
rearrangement of the nuclear pores could
account for the relaxation of chromatin
constraint on long timescales. The idea
that chromatin diffusion is constrained via
interactions with the NE is supported by
two recent studies that found that diffusion
of chromatin loci associated with the NE is
signiFcantly more constrained than other
loci. In the most dramatic example, Chubb
and coworkers showed that NE-associated
chromatin has exactly the same diffusion
constant as other chromatin, but is con-
Fned to a much smaller subregion of the
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