Cell News 01/2017
19
BINDER INNOVATION PRIZE 2017
We analyzed the effect of mechanical strain on transcription
(A) and observed global transcriptional repression (B) with
specific enrichment of polycomb repressive complex 2 (PRC2)
target gene downregulation through gain of H3K27me3 (C, D),
leading to inhibition of lineage progression gene expression (E).
Intriguingly, at the same time lamina-associated domains lost
H3K9me3, which was replaced by H3K27me3 to maintain si-
lencing of these regions (F). The changes in gene silencing were
induced by a mechanosensitive switch at the nuclear lamina:
assembly of a stress-dissipating, contractile perinuclear actin
ring and remodeling of the emerin-containing stiff nuclear lam-
ina meshwork. This was accompanied by large-scale chromatin
rearrangements as visualized with whole chromosome FISH
for Chromosomes (Chr) 1 and 18 (G). Our work indicates that
mechanical strain promotes a switch from a lamina-associated
H3K9me3 state of heterochromatin to a state characterized by
perinuclear actin and more loosely packed and lamina-disasso-
ciated H3K27me3 allowing mechanoadaptation. Modified from
Le et al., 2016.
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Figure 3: Transcriptional and rheological adaptation of the nucleus through regulation of the nuclear lamina
and chromatin.
