The histone chaperone FACT facilitates heterochromatin spreading by regulating histone turnover and H3K9 methylation states.

Aminopeptidases / genetics Cell Cycle Proteins / genetics Chromatin Assembly and Disassembly Gene Expression Regulation, Fungal Gene Silencing Heterochromatin / genetics Histone Chaperones / genetics Histone-Lysine N-Methyltransferase / genetics Histones / metabolism Methylation Mutation Nuclear Proteins / genetics Protein Processing, Post-Translational Schizosaccharomyces / genetics Schizosaccharomyces pombe Proteins / genetics Transcription, Genetic
Epe1 FACT heterochromatin spreading histone chaperone histone turnover

Journal

Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691

Informations de publication

Date de publication:
02 11 2021
Historique:
received: 19 07 2021
revised: 14 09 2021
accepted: 13 10 2021
entrez: 3 11 2021
pubmed: 4 11 2021
medline: 16 2 2022
Statut: ppublish

Résumé

Heterochromatin formation requires three distinct steps: nucleation, self-propagation (spreading) along the chromosome, and faithful maintenance after each replication cycle. Impeding any of those steps induces heterochromatin defects and improper gene expression. The essential histone chaperone FACT (facilitates chromatin transcription) has been implicated in heterochromatin silencing, but the mechanisms by which FACT engages in this process remain opaque. Here, we pinpoint its function to the heterochromatin spreading process in fission yeast. FACT impairment reduces nucleation-distal H3K9me3 and HP1/Swi6 accumulation at subtelomeres and derepresses genes in the vicinity of heterochromatin boundaries. FACT promotes spreading by repressing heterochromatic histone turnover, which is crucial for the H3K9me2 to me3 transition that enables spreading. FACT mutant spreading defects are suppressed by removal of the H3K9 methylation antagonist Epe1. Together, our study identifies FACT as a histone chaperone that promotes heterochromatin spreading and lends support to the model that regulated histone turnover controls the propagation of repressive methylation marks.

Identifiants

DOI: 10.1016/j.celrep.2021.109944 PMID: 34731638 PMC: PMC8608617
pubmed: 34731638
pii: S2211-1247(21)01417-0
doi: 10.1016/j.celrep.2021.109944
pmc: PMC8608617
mid: NIHMS1753646
pii:
doi:

Substances chimiques

Cell Cycle Proteins 0
Heterochromatin 0
Histone Chaperones 0
Histones 0
Nuclear Proteins 0
Schizosaccharomyces pombe Proteins 0
epe1 protein, S pombe 0
Histone-Lysine N-Methyltransferase EC 2.1.1.43
clr4 protein, S pombe EC 2.1.1.43
Aminopeptidases EC 3.4.11.-
Spt16 protein, S pombe EC 3.4.11.9

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

109944

Subventions

Organisme : NIGMS NIH HHS
ID : DP2 GM123484
Pays : United States
Organisme : NIGMS NIH HHS
ID : R35 GM141888
Pays : United States

Informations de copyright

Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests A.G.L. is a founder, CSO, shareholder, and managing director of Eisbach Bio GmbH, a biotechnology company developing cancer medicines. All other authors declare no competing interests.

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Auteurs

Magdalena Murawska (M)

Physiological Chemistry, Biomedical Center, Faculty of Medicine, Ludwig-Maximilians-University Munich, 82152 Planegg-Martinsried, Germany. Electronic address: magdalena.murawska@bmc.med.lmu.de.

R A Greenstein (RA)

Department of Microbiology and Immunology, University of California, San Francisco, CA 94143, USA; George Williams Hooper Research Foundation, University of California, San Francisco, CA 94143, USA; TETRAD Graduate Program, University of California, San Francisco, CA 94143, USA.

Tamas Schauer (T)

Bioinformatics Unit, Biomedical Center, Faculty of Medicine, Ludwig-Maximilians-University Munich, 82152 Planegg-Martinsried, Germany.

Karl C F Olsen (KCF)

Physiological Chemistry, Biomedical Center, Faculty of Medicine, Ludwig-Maximilians-University Munich, 82152 Planegg-Martinsried, Germany; International Max Planck Research School for Molecular and Cellular Life Sciences, 82152 Planegg-Martinsried, Germany.

Henry Ng (H)

Department of Microbiology and Immunology, University of California, San Francisco, CA 94143, USA; George Williams Hooper Research Foundation, University of California, San Francisco, CA 94143, USA; TETRAD Graduate Program, University of California, San Francisco, CA 94143, USA.

Andreas G Ladurner (AG)

Physiological Chemistry, Biomedical Center, Faculty of Medicine, Ludwig-Maximilians-University Munich, 82152 Planegg-Martinsried, Germany; International Max Planck Research School for Molecular and Cellular Life Sciences, 82152 Planegg-Martinsried, Germany.

Bassem Al-Sady (B)

Department of Microbiology and Immunology, University of California, San Francisco, CA 94143, USA; George Williams Hooper Research Foundation, University of California, San Francisco, CA 94143, USA. Electronic address: bassem.al-sady@ucsf.edu.

Sigurd Braun (S)

Physiological Chemistry, Biomedical Center, Faculty of Medicine, Ludwig-Maximilians-University Munich, 82152 Planegg-Martinsried, Germany; International Max Planck Research School for Molecular and Cellular Life Sciences, 82152 Planegg-Martinsried, Germany; Institute for Genetics, Justus-Liebig University Giessen, 35392 Giessen, Germany. Electronic address: sigurd.braun@gen.bio.uni-giessen.de.

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Classifications MeSH

questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Hydrolases › Peptide hydrolases › Exopeptidases › Aminopeptidases › The histone chaperone FACT facilitates...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines du cycle cellulaire › The histone chaperone FACT facilitates...
questionsmedicales.fr › Phénomènes génétiques › Régulation de l'expression des gènes › Assemblage et désassemblage de la chromatine › The histone chaperone FACT facilitates...
questionsmedicales.fr › Phénomènes génétiques › Régulation de l'expression des gènes › Régulation de l'expression des gènes fongiques › The histone chaperone FACT facilitates...
questionsmedicales.fr › Phénomènes génétiques › Régulation de l'expression des gènes › Épigenèse génétique › Extinction de l'expression des gènes › The histone chaperone FACT facilitates...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Structures de chromosome › Chromatine › Hétérochromatine › The histone chaperone FACT facilitates...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Chaperons moléculaires › Chaperons d'histones › The histone chaperone FACT facilitates...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Transferases › One-carbon group transferases › Methyltransferases › Protein Methyltransferases › Histone méthyltransférases › Histone-lysine N-methyltransferase › The histone chaperone FACT facilitates...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Nucléoprotéines › Histone › The histone chaperone FACT facilitates...
questionsmedicales.fr › Métabolisme › Alkylation › Méthylation › The histone chaperone FACT facilitates...
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Mutation › The histone chaperone FACT facilitates...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines nucléaires › The histone chaperone FACT facilitates...
questionsmedicales.fr › Phénomènes génétiques › Régulation de l'expression des gènes › Modification traductionnelle des protéines › Maturation post-traductionnelle des protéines › The histone chaperone FACT facilitates...
questionsmedicales.fr › Eucaryotes › Champignons › Levures › Schizosaccharomyces › The histone chaperone FACT facilitates...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines fongiques › Protéines de Schizosaccharomyces pombe › The histone chaperone FACT facilitates...
questionsmedicales.fr › Phénomènes génétiques › Expression des gènes › Transcription génétique › The histone chaperone FACT facilitates...