Molecular Biology of the Cell by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morgan, Martin Raff, Keith Roberts, Peter Walter by by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morg

CHROMATIN STRUCTURE AND FUNCTION
205
histone
modification
heterochromatin proteins
heterochromatin
nucleosomes
euchromatin
CHROMOSOME
DUPLICATION
NEW HETEROCHROMATIN
PROTEINS ADDED TO REGION
WITH MODIFIED HISTONES
Figure 4–44 How the packaging of
DNA in chromatin can be inherited
following chromosome replication.
In this model, some of the specialized
chromatin components are distributed
to each sister chromosome after DNA
duplication, along with the specially marked
nucleosomes that they bind. After DNA
replication, the inherited nucleosomes that
are specially modified, acting in concert
with the inherited chromatin components,
change the pattern of histone modification
on the newly formed nucleosomes nearby.
This creates new binding sites for the
same chromatin components, which then
assemble to complete the structure. The
latter process is likely to involve reader–
writer–remodeling complexes operating in a
manner similar to that previously illustrated
in Figure 4–40.
heterochromatin euchromatin heterochromatin euchromatin
heterochromatin. In particular, the entire centromere forms as an all-or-none
entity, suggesting that the creation of centromeric chromatin is a highly cooperative
process, spreading out from an initial seed in a manner reminiscent of
the phenomenon of position effect variegation that we discussed earlier. In both
cases, a particular chromatin structure, once formed, seems to be directly inherited
on the DNA following each round of chromosome replication. A cooperative
recruitment of proteins, along with the action of reader–writer complexes, can
thus not only account for the spreading
MBoC6 m4.52/4.44
of specific forms of chromatin in space
along the chromosome, but also for its propagation across cell generations—from
parent cell to daughter cell (Figure 4–44).
Experiments with Frog Embryos Suggest that both Activating and
Repressive Chromatin Structures Can Be Inherited Epigenetically
Epigenetic inheritance plays a central part in the creation of multicellular organisms.
Their differentiated cell types become established during development, and
persist thereafter even through repeated cell-division cycles. The daughters of a
liver cell persist as liver cells, those of an epidermal cell as epidermal cells, and so
on, even though they all contain the same genome; and this is because distinctive
patterns of gene expression are passed on faithfully from parent cell to daughter
cell. Chromatin structure has a role in this epigenetic transmission of information
from one cell generation to the next.
One type of evidence comes from studies in which the nucleus of a cell from
a frog or tadpole is transplanted into a frog egg whose own nucleus has been
removed (an enucleated egg). In a classic set of experiments performed in 1968,
it was shown that a nucleus taken from a differentiated donor cell can be reprogrammed
in this way to support development of a whole new tadpole (see Figure
7–2). But this reprogramming occurs only with difficulty, and it becomes less and
less efficient as nuclei from older animals are used. Thus, for example, less than
2% of the enucleated eggs injected with a nucleus from a tadpole epithelial cell
developed to the swimming tadpole stage, compared with 35% when the donor
nuclei were taken instead from an early (gastrula-stage) embryo. With new experimental
tools, the cause of this resistance to reprogramming can now be traced.
It arises, at least in part, because specific chromatin structures in the original differentiated
nucleus tend to persist and be transmitted through the many cell-division
cycles required for embryonic development. In experiments with Xenopus
embryos, specific forms of either repressive or active chromatin structures could
be demonstrated to persist through as many as 24 cell divisions, causing the misplaced
expression of genes. Figure 4–45 briefly describes one such experiment,