Biology Reference
In-Depth Information
3.6. Heterochromatin assembly: A more general RNA-related
mechanism also in mammals?
More generally, it is reasonable to say that ncRNAmolecules of various sizes
appear to play a major role in the regulation of silent chromatin biology. For
example, RNAs play an important role in chromosome-specific localization
of the activities of chromatin modifiers required for dosage compensation in
Drosophila
and mammals (
Park & Kuroda, 2001
) and also in some cases of
genomic imprinting (
Sleutels, Zwart, & Barlow, 2002
). In mammals,
Xist
RNA originating from the X-inactivation center is required for initiation
but not for the subsequent inheritance of X-inactivation (
Avner & Heard,
2001
), and silencing is also regulated by
Tsix
,an
Xist
antisense transcript
(
Cohen & Lee, 2002
). Interestingly, it has been recently shown that long
interspersed repeated elements (LINEs) that are enriched on the X chromo-
some comparedwith autosomes (
Boyle, Ballard, &Ward, 1990
) participate in
creating a silent nuclear compartment into which X-linked genes become
recruited. These LINE repeats contain a subset of “young” LINE-1 elements
that are therefore relatively active and expressed duringX-inactivation, rather
than being silenced. Expression of these LINEs requires the specific hetero-
chromatic state induced by
Xist
. These LINEs often lie within escape-prone
regions of the X chromosome, but close to the genes that are subject to
X-inactivation, and are associated with putative endo-siRNAs. LINEs may
thus facilitate X-inactivation at different levels, with silent LINEs participat-
ing in assembly of a heterochromatic nuclear compartment induced by
Xist
,
and active LINEs participating in local propagation of X-inactivation into
regions that would otherwise be prone to escape (
Chow et al., 2010
).
It is possible that other repetitive elements in the mammalian genome, in
particular, retrotransposons, can function as nucleators of silent compart-
ments and/or as spreading or antispreading mechanisms for heterochroma-
tin. In most differentiated cells, such repetitive elements are fully silenced to
avoid phenomena such as retrotransposition and recombination that would
otherwise compromise DNA integrity (
Maksakova, Mager, & Reiss, 2008
).
As mentioned earlier, the lack of conventional heterochromatic modifica-
tions during the earliest stages of embryogenesis has been suggested to pro-
vide a window of opportunity for the reactivation of nondesired 'guests' in
the genome like retrotransposons. Indeed, transcripts derived from repeti-
tive elements are found in the early embryo (
Bachvarova, 1988; Efroni
et al., 2008; Evsikov et al., 2004; Packer, Manova, & Bachvarova, 1993;
Peaston et al., 2004
). We have recently found that the transcriptional acti-
vationof these elements decreases at the 8-cell stage after a peak of reactivation
