Biology Reference
In-Depth Information
new organism. However, this amazing capacity of the cells in the mouse
embryo to generate all cell types seems to be transient as transplantation exper-
iments have shown that cells from the ICM of a late blastocyst no longer have
the potential to form trophectodermderivatives (
Rossant &Lis, 1979
). Indeed,
the ability of the early embryo to reprogram somatic nuclei decreases as devel-
opment proceeds (
Eckardt, Leu, Kurosaka, & McLaughlin, 2005
), suggesting
that the capacity to reprogram to totipotency also decreases during time.
What makes the cells in the early embryo capable of supporting such a
large degree of plasticity? How is this plastic state achieved after fertilization
and how is this state maintained in the early embryo? These questions have
remained largely unanswered and are central for our understanding of cell
plasticity, development, and reprogramming. We propose that the basis
of such plasticity relies—at least partially—on the distinctive heterochroma-
tin features that prevail during early embryogenesis. Here, we will review
some of these major features and discuss recent findings that have shed some
light on the mechanisms driving heterochromatin formation after fertiliza-
tion, in particular, in light of what is known in other model systems where
we have a more in depth mechanistic knowledge on the formation and
maintenance of heterochromatin. Finally, we will put forward some of
the questions that in our view represent the major key challenges to address
in the field for the coming years.
2. HETEROCHROMATIN IN THE EARLY EMBRYO:
A RATHER PARTICULAR ENVIRONMENT
Addressing the mechanisms behind the establishment of heterochro-
matin during the development of preimplantation mouse embryos is partic-
ularly relevant because of the huge changes on the chromatin that occur after
fertilization. Indeed, most chromatin signatures have to be established
de novo
at the start of development. Because of this, the mouse embryo is
one of the few model systems that offer the possibility of dissecting the
mechanisms that underlie the establishment of heterochromatin in mam-
mals, as opposed to studying heterochromatin maintenance and/or spread-
ing in somatic cells, where heterochromatin only has to be maintained.
Perhaps most interestingly, the question of whether a global rearrangement
of heterochromatin and its structure impact on cell potency and develop-
ment is a very attractive one.
Histones can be posttranslationally modified, and this provides an impor-
tant level of functionality to the chromatin (
Kouzarides, 2007; Strahl & Allis,
