Cell
Volume 163, Issue 6, 3 December 2015, Pages 1333-1347
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Article
Perinuclear Anchoring of H3K9-Methylated Chromatin Stabilizes Induced Cell Fate in C. elegans Embryos

https://doi.org/10.1016/j.cell.2015.10.066Get rights and content
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Highlights

  • C. elegans chromodomain protein CEC-4 associates stably with the nuclear envelope

  • CEC-4 anchors heterochromatin through recognition of methylated H3K9 in embryos

  • Unlike loss of H3K9 methylation, cec-4 mutant does not alter gene expression

  • cec-4 loss abrogates the embryo’s ability to maintain an induced muscle cell fate

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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Present address: Department of Molecular Cell Biology, The Weizmann Institute of Science, Rehovot 76100, Israel