Biology Reference
In-Depth Information
provide the specificity for targeting histone-modifying activities to the
corresponding genomic location in which they are generated.
Inmammals, it has recently been suggested that some transcription factors
could act as repressors of heterochromatic pericentromeric repeats and
thereby regulate heterochromatic signatures at those repeats (
Bulut-
Karslioglu et al., 2012
). However, it is not yet clear whether this is a gen-
eralized mechanism and/or whether the establishment of heterochromatin
after fertilization obeys a potential nucleation step that depends upon a tran-
scription factor. In any case, the general agreement suggests that it is the tran-
scripts themselves that are generated from heterochromatic-to-be loci that
function as initial nuleators of heterochromatin formation.
3.5. Establishment of pericentric heterochromatin in mammals
In mammalian cells, transcription of major satellite repeats occurs during
S-phase, and their transcription seems to take place before replication of
the heterochromatic sequences (
Lu & Gilbert, 2007
). Their transcription is
induced in response to cell proliferation and may involve H3S10P or disso-
ciation of HP1 proteins triggered by specific signals during the cell cycle. But
it has also been reported that gamma-satellite sequences (e.g., major satellite
sequences) are repressed upon retinoic acid treatment (
Rudert, Bronner,
Garnier, & Dolle, 1995
). Inducing muscle differentiation using C2C12 cells
has also revealed that differentiation is accompaniedby a spatial reorganization
of constitutive pericentromeric repeats, that is, associatedwith elevatedmajor
and minor satellite transcripts (
Terranova, Sauer, Merkenschlager, & Fisher,
2005
).Contrastingwith these results, EScell differentiation inducedby retinoic
acid has been shown to result in increased accumulation or major satellite tran-
scripts (
Martens et al., 2005
). Thus, although there are a few reports docu-
menting major satellite transcription in mammalian cells, the physiological
and differentiation contexts of such reports are varied and it seems difficult
to reconcile a potential unique function to those observations. In particular,
it is not known whether S-phase transcription facilitates heterochromatin
assembly in a manner similar to the process of transcription-coupled establish-
ment of silenced chromatin in fission yeast that we described earlier.
Recent analyses in early mouse embryos have attempted to investigate
whether transcription of pericentromeric repeats is functionally linked to het-
erochromatin formation in mammals. Work by Almouzni and colleagues
documented a very precise temporal regulation of major satellite transcription
following fertilization (
Probst et al., 2010
). Transcription from both forward
