Biology Reference
In-Depth Information
the cells in the early embryo relies on the distinctive heterochromatin features that pre-
vail during early embryogenesis. Here, we review some of these features and discuss
recent findings on the mechanisms driving heterochromatin formation after fertilization,
in particular, the emerging role of RNA as a regulator of heterochromatic loci also in
mammals. Finally, we believe that there are at least three major avenues that should
be addressed in the coming years: (i) Is heterochromatin a driving force in development?
(ii) Does it have a role in lineage allocation? (iii) How can heterochromatin
“
regulate
”
epigenetic reprogramming?
1. INTRODUCTION
Embryonic development is a specificity of metazoans. It starts with the
fertilization of the oocyte by a sperm. Following fertilization, the gametes
undergo intense chromatin remodeling and epigenetic reprogramming,
which is necessary to revert into a totipotent state, essential to start a newdevel-
opmental program. Importantly, in its natural context, such reprogramming
should occur with 100% efficiency in order to sustain development.
In mammals, fertilization is followed by a series of successive divisions
during which the embryo generates a higher cell number but maintains
the same size overall until the blastocyst stage. The early blastocyst is com-
posed of two lineages: the pluripotent cells of the inner cell mass (ICM),
which will give rise to the embryo proper, and the trophectoderm, which
will give rise to the placenta and is considered the first differentiated tissue in
the embryo. A third lineage, the primitive endoderm, which is extraembry-
onic, emerges by the late blastocyst stage. After implantation of the blastocyst
into the uterine wall, the embryo undergoes gastrulation, during which the
three germ layers of the embryo are established and will be complemented
by subsequent somitogenesis and organogenesis. During all these develop-
mental processes, the structure of the chromatin is expected to be largely
remodeled and modified. The changes to the structure of the chromatin
are thought to have a direct effect on gene expression and therefore a key
role in the control of developmental gene expression or repression.
In eukaryotic cells, the DNA is organized into chromatin, which regulates
the accessibility of the genetic information. The building block of the chroma-
tin is the nucleosome, which consists of two copies of each of the core histones
H2A, H2B, H3, and H4 wrapped with
146 bp of DNA (
Luger, Mader,
Richmond, Sargent, & Richmond, 1997
). The histones are subject to an
increasing number of covalent modifications such as methylation and acetyla-
tion, which have been shown to regulate chromatin-mediated processes in
