  Despite their dynamic nature, certain chromatin marks must be maintained over
the long term. This is particulary true for histone 3 lysine 9 (H3K9)
trimethylation, that is involved in the maintenance of healthy differentiated
cellular states by preventing inappropriate gene expression, and has been
recently identified as the most efficient barrier to cellular reprogramming in
nuclear transfer experiments. We propose that the capacity of the enzymes
SUV39H1/2 to rebind to a minor fraction of their products, either directly or
via HP1, contributes to the solidity of this mark through (i) a positive
feedback involved in its establishment by the mutual enforcement of H3K9me3 and
SUV39H1/2 and then (ii) a negative feedback sufficient to strongly stabilize
H3K9me3 heterochromatin in post-mitotic cells by generating local enzyme
concentrations capable of counteracting transient bursts of demethylation. This
model does not require direct molecular interactions with adjacent nucleosomes
and is favoured by a series of additional mechanisms including (i) the
protection of chromatin-bound SUV39H1/2 from the turnovers of soluble proteins,
which can explain the uncoupling between the cellular contents in SUV39H1 mRNA
and protein; (ii) the cooperative dependence on the local density of the
H3K9me3 of HP1-dependent heterochomatin condensation and, dispensably (iii)
restricted enzyme exchanges with chromocenters confining the reactive bursts of
SUV39H1/2 in heterochromatin. This mechanism illustrates how seemingly static
epigenetic states can be firmly maintained by dynamic and reversible
modifications.
