[PDF][PDF] Perinuclear anchoring of H3K9-methylated chromatin stabilizes induced cell fate in C. elegans embryos

A Gonzalez-Sandoval, BD Towbin, V Kalck… - Cell, 2015 - cell.com
A Gonzalez-Sandoval, BD Towbin, V Kalck, DS Cabianca, D Gaidatzis, MH Hauer, L Geng…
Cell, 2015cell.com
Interphase chromatin is organized in distinct nuclear sub-compartments, reflecting its degree
of compaction and transcriptional status. In Caenorhabditis elegans embryos, H3K9
methylation is necessary to silence and to anchor repeat-rich heterochromatin at the nuclear
periphery. In a screen for perinuclear anchors of heterochromatin, we identified a previously
uncharacterized C. elegans chromodomain protein, CEC-4. CEC-4 binds preferentially
mono-, di-, or tri-methylated H3K9 and localizes at the nuclear envelope independently of …
Summary
Interphase chromatin is organized in distinct nuclear sub-compartments, reflecting its degree of compaction and transcriptional status. In Caenorhabditis elegans embryos, H3K9 methylation is necessary to silence and to anchor repeat-rich heterochromatin at the nuclear periphery. In a screen for perinuclear anchors of heterochromatin, we identified a previously uncharacterized C. elegans chromodomain protein, CEC-4. CEC-4 binds preferentially mono-, di-, or tri-methylated H3K9 and localizes at the nuclear envelope independently of H3K9 methylation and nuclear lamin. CEC-4 is necessary for endogenous heterochromatin anchoring, but not for transcriptional repression, in contrast to other known H3K9 methyl-binders in worms, which mediate gene repression but not perinuclear anchoring. When we ectopically induce a muscle differentiation program in embryos, cec-4 mutants fail to commit fully to muscle cell fate. This suggests that perinuclear sequestration of chromatin during development helps restrict cell differentiation programs by stabilizing commitment to a specific cell fate.
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