title: Global regulation of heterochromatin spreading by Leo1.
abstract: Heterochromatin plays important roles in eukaryotic genome regulation. However, the repressive nature of heterochromatin combined with its propensity to self-propagate necessitates robust mechanisms to contain heterochromatin within defined boundaries and thus prevent silencing of expressed genes. Here we show that loss of the PAF complex (PAFc) component Leo1 compromises chromatin boundaries, resulting in invasion of heterochromatin into flanking euchromatin domains. Similar effects are seen upon deletion of other PAFc components, but not other factors with related functions in transcription-associated chromatin modification, indicating a specific role for PAFc in heterochromatin regulation. Loss of Leo1 results in reduced levels of H4K16 acetylation at boundary regions, while tethering of the H4K16 acetyltransferase Mst1 to boundary chromatin suppresses heterochromatin spreading in leo1Δ cells, suggesting that Leo1 antagonises heterochromatin spreading by promoting H4K16 acetylation. Our findings reveal a previously undescribed role for PAFc in regulating global heterochromatin distribution.
authors.affiliation: Institute of Cell Biology, University of Edinburgh, Edinburgh, UK.
authors.forename: Laure
authors.initials: L
authors.lastname: Verrier
authors.affiliation: Institute of Cell Biology, University of Edinburgh, Edinburgh, UK.
authors.forename: Francesca
authors.initials: F
authors.lastname: Taglini
authors.affiliation: Butenandt Institute of Physiological Chemistry, Ludwig-Maximilians-Universität München, Munich, Germany.
authors.forename: Ramon R
authors.initials: RR
authors.lastname: Barrales
authors.affiliation: Wellcome Trust Centre for Cell Biology, School of Biological Sciences, University of Edinburgh, Edinburgh, UK.
authors.forename: Shaun
authors.initials: S
authors.lastname: Webb
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Shimane University, Izumo, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Urano
authors.affiliation: Butenandt Institute of Physiological Chemistry, Ludwig-Maximilians-Universität München, Munich, Germany.
authors.forename: Sigurd
authors.initials: S
authors.lastname: Braun
authors.affiliation: Institute of Cell Biology, University of Edinburgh, Edinburgh, UK elizabeth.bayne@ed.ac.uk.
authors.forename: Elizabeth H
authors.initials: EH
authors.lastname: Bayne
mesh_terms: D000107:Acetylation; D001665:Binding Sites; D047369:Chromatin Immunoprecipitation; D015966:Gene Expression Regulation, Fungal; D023061:Gene Order; D016681:Genome, Fungal; D006570:Heterochromatin / Q000235:genetics* / Q000378:metabolism*; D059014:High-Throughput Nucleotide Sequencing; D006657:Histones / Q000378:metabolism; D055029:Inverted Repeat Sequences; D011485:Protein Binding; D016601:RNA-Binding Proteins / Q000378:metabolism*; D012568:Schizosaccharomyces / Q000235:genetics / Q000378:metabolism
chemical_list: D006570:Heterochromatin; D006657:Histones; D016601:RNA-Binding Proteins
keywords: Leo1; epigenetics; fission yeast; genome regulation; heterochromatin