title: A nucleosome turnover map reveals that the stability of histone H4 Lys20 methylation depends on histone recycling in transcribed chromatin.
abstract: Nucleosome composition actively contributes to chromatin structure and accessibility. Cells have developed mechanisms to remove or recycle histones, generating a landscape of differentially aged nucleosomes. This study aimed to create a high-resolution, genome-wide map of nucleosome turnover in Schizosaccharomyces pombe. The recombination-induced tag exchange (RITE) method was used to study replication-independent nucleosome turnover through the appearance of new histone H3 and the disappearance or preservation of old histone H3. The genome-wide location of histones was determined by chromatin immunoprecipitation-exonuclease methodology (ChIP-exo). The findings were compared with diverse chromatin marks, including histone variant H2A.Z, post-translational histone modifications, and Pol II binding. Finally, genome-wide mapping of the methylation states of H4K20 was performed to determine the relationship between methylation (mono, di, and tri) of this residue and nucleosome turnover. Our analysis showed that histone recycling resulted in low nucleosome turnover in the coding regions of active genes, stably expressed at intermediate levels. High levels of transcription resulted in the incorporation of new histones primarily at the end of transcribed units. H4K20 was methylated in low-turnover nucleosomes in euchromatic regions, notably in the coding regions of long genes that were expressed at low levels. This transcription-dependent accumulation of histone methylation was dependent on the histone chaperone complex FACT. Our data showed that nucleosome turnover is highly dynamic in the genome and that several mechanisms are at play to either maintain or suppress stability. In particular, we found that FACT-associated transcription conserves histones by recycling them and is required for progressive H4K20 methylation.
authors.affiliation: Department of Biosciences and Nutrition, Karolinska Institutet, Novum, 141 57 Huddinge, Sweden;
authors.forename: J Peter
authors.initials: JP
authors.lastname: Svensson
authors.affiliation: Wellcome Trust Centre for Cell Biology, School of Biological Sciences, The University of Edinburgh, Edinburgh EH9 3JR, Scotland, United Kingdom;
authors.forename: Manu
authors.initials: M
authors.lastname: Shukla
authors.affiliation: Department of Biosciences and Nutrition, Karolinska Institutet, Novum, 141 57 Huddinge, Sweden;
authors.forename: Victoria
authors.initials: V
authors.lastname: Menendez-Benito
authors.affiliation: Department of Biosciences and Nutrition, Karolinska Institutet, Novum, 141 57 Huddinge, Sweden;
authors.forename: Ulrika
authors.initials: U
authors.lastname: Norman-Axelsson
authors.affiliation: Wellcome Trust Centre for Cell Biology, School of Biological Sciences, The University of Edinburgh, Edinburgh EH9 3JR, Scotland, United Kingdom;
authors.forename: Pauline
authors.initials: P
authors.lastname: Audergon
authors.affiliation: Department of Biosciences and Nutrition, Karolinska Institutet, Novum, 141 57 Huddinge, Sweden;
authors.forename: Indranil
authors.initials: I
authors.lastname: Sinha
authors.affiliation: Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec H3G 1Y6, Canada.
authors.forename: Jason C
authors.initials: JC
authors.lastname: Tanny
authors.affiliation: Wellcome Trust Centre for Cell Biology, School of Biological Sciences, The University of Edinburgh, Edinburgh EH9 3JR, Scotland, United Kingdom;
authors.forename: Robin C
authors.initials: RC
authors.lastname: Allshire
authors.affiliation: Department of Biosciences and Nutrition, Karolinska Institutet, Novum, 141 57 Huddinge, Sweden;
authors.forename: Karl
authors.initials: K
authors.lastname: Ekwall
mesh_terms: D047369:Chromatin Immunoprecipitation; D004261:DNA Replication; D030541:Databases, Genetic; D056726:Genetic Association Studies; D016681:Genome, Fungal; D006657:Histones / Q000235:genetics* / Q000378:metabolism; D008745:Methylation; D046228:Microarray Analysis; D009707:Nucleosomes / Q000235:genetics* / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D012568:Schizosaccharomyces / Q000235:genetics* / Q000378:metabolism
chemical_list: D006657:Histones; D009707:Nucleosomes