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Perinuclear Anchoring of H3K9-Methylated Chromatin Stabilizes Induced Cell Fate in C. elegans Embryos

Gonzalez-Sandoval, Adriana and D. Towbin, Benjamin and Gaidatzis, Dimos and Geng, Liqing and Wang, Li and Yang, Teddy and Zhao, Kehao and Gasser, Susan (2015) Perinuclear Anchoring of H3K9-Methylated Chromatin Stabilizes Induced Cell Fate in C. elegans Embryos. Cell.

Abstract

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.

Item Type: Article
Additional Information: Running title: Perinuclear chromodomain protein anchors heterochromatin
Keywords: C. elegans, heterochromatin, nuclear envelope anchoring, H3K9 methylation
Date Deposited: 03 May 2016 23:45
Last Modified: 03 May 2016 23:45
URI: https://oak.novartis.com/id/eprint/10666

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