title: Perinuclear Anchoring of H3K9-Methylated Chromatin Stabilizes Induced Cell Fate in C. elegans Embryos.
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. PAPERCLIP.
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, CH-4058 Basel, Switzerland; Faculty of Natural Sciences, University of Basel, Klingelbergstrasse 50/70, CH-4056 Basel, Switzerland.
authors.forename: Adriana
authors.initials: A
authors.lastname: Gonzalez-Sandoval
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, CH-4058 Basel, Switzerland.
authors.forename: Benjamin D
authors.initials: BD
authors.lastname: Towbin
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, CH-4058 Basel, Switzerland.
authors.forename: Veronique
authors.initials: V
authors.lastname: Kalck
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, CH-4058 Basel, Switzerland.
authors.forename: Daphne S
authors.initials: DS
authors.lastname: Cabianca
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, CH-4058 Basel, Switzerland; Swiss Institute of Bioinformatics, CH-4058 Basel, Switzerland.
authors.forename: Dimos
authors.initials: D
authors.lastname: Gaidatzis
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, CH-4058 Basel, Switzerland; Faculty of Natural Sciences, University of Basel, Klingelbergstrasse 50/70, CH-4056 Basel, Switzerland.
authors.forename: Michael H
authors.initials: MH
authors.lastname: Hauer
authors.affiliation: China Novartis Institute of Biomedical Research Co, Ltd. Bldg 3, Lane 3728 Jinke Road, Pudong New Area, Shanghai 201203, China.
authors.forename: Liqing
authors.initials: L
authors.lastname: Geng
authors.affiliation: China Novartis Institute of Biomedical Research Co, Ltd. Bldg 3, Lane 3728 Jinke Road, Pudong New Area, Shanghai 201203, China.
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.affiliation: China Novartis Institute of Biomedical Research Co, Ltd. Bldg 3, Lane 3728 Jinke Road, Pudong New Area, Shanghai 201203, China.
authors.forename: Teddy
authors.initials: T
authors.lastname: Yang
authors.affiliation: China Novartis Institute of Biomedical Research Co, Ltd. Bldg 3, Lane 3728 Jinke Road, Pudong New Area, Shanghai 201203, China.
authors.forename: Xinghao
authors.initials: X
authors.lastname: Wang
authors.affiliation: China Novartis Institute of Biomedical Research Co, Ltd. Bldg 3, Lane 3728 Jinke Road, Pudong New Area, Shanghai 201203, China.
authors.forename: Kehao
authors.initials: K
authors.lastname: Zhao
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, CH-4058 Basel, Switzerland; Faculty of Natural Sciences, University of Basel, Klingelbergstrasse 50/70, CH-4056 Basel, Switzerland. Electronic address: susan.gasser@fmi.ch.
authors.forename: Susan M
authors.initials: SM
authors.lastname: Gasser
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans / Q000166:cytology / Q000196:embryology* / Q000235:genetics* / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004625:Embryo, Nonmammalian / Q000166:cytology* / Q000378:metabolism; D006570:Heterochromatin; D042421:Histone Code; D008969:Molecular Sequence Data; D016415:Sequence Alignment
chemical_list: C000606331:CEC-4 protein, C elegans; D029742:Caenorhabditis elegans Proteins; D002868:Chromosomal Proteins, Non-Histone; D006570:Heterochromatin