title: Restriction of Retrotransposon Mobilization in Schizosaccharomyces pombe by Transcriptional Silencing and Higher-Order Chromatin Organization.
abstract: Uncontrolled propagation of retrotransposons is potentially detrimental to host genome integrity. Therefore, cells have evolved surveillance mechanisms to restrict the mobility of these elements. In Schizosaccharomyces pombe the Tf2 LTR retrotransposons are transcriptionally silenced and are also clustered in the nucleus into structures termed Tf bodies. Here we describe the impact of silencing and clustering on the mobility of an endogenous Tf2 element. Deletion of genes such as set1(+) (histone H3 lysine 4 methyltransferase) or abp1(+) (CENP-B homolog) that both alleviate silencing and clustering, result in a corresponding increase in mobilization. Furthermore, expression of constitutively active Sre1, a transcriptional activator of Tf2 elements, also alleviates clustering and induces mobilization. In contrast, clustering is not disrupted by loss of the HIRA histone chaperone, despite high levels of expression, and in this background, mobilization frequency is only marginally increased. Thus, mutations that compromise transcriptional silencing but not Tf bodies are insufficient to drive mobilization. Furthermore, analyses of mutant alleles that separate the transcriptional repression and clustering functions of Set1 are consistent with control of Tf2 propagation via a combination of silencing and spatial organization. Our results indicate that host surveillance mechanisms operate at multiple levels to restrict Tf2 retrotransposon mobilization.
authors.affiliation: Institute for Cell and Molecular Biosciences, Newcastle University, Newcastle upon Tyne, NE2 4HH, United Kingdom.
authors.forename: Heather E
authors.initials: HE
authors.lastname: Murton
authors.affiliation: Biology Department, Boston College, Chestnut Hill, Massachusetts 02467.
authors.forename: Patrick J R
authors.initials: PJ
authors.lastname: Grady
authors.affiliation: Institute for Cell and Molecular Biosciences, Newcastle University, Newcastle upon Tyne, NE2 4HH, United Kingdom.
authors.forename: Tsun Ho
authors.initials: TH
authors.lastname: Chan
authors.affiliation: Biology Department, Boston College, Chestnut Hill, Massachusetts 02467 hugh.cam@bc.edu simon.whitehall@ncl.ac.uk.
authors.forename: Hugh P
authors.initials: HP
authors.lastname: Cam
authors.affiliation: Institute for Cell and Molecular Biosciences, Newcastle University, Newcastle upon Tyne, NE2 4HH, United Kingdom hugh.cam@bc.edu simon.whitehall@ncl.ac.uk.
authors.forename: Simon K
authors.initials: SK
authors.lastname: Whitehall
mesh_terms: D002843:Chromatin / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D015966:Gene Expression Regulation, Fungal; D016681:Genome, Fungal; D042822:Genomic Instability; D011495:Histone-Lysine N-Methyltransferase / Q000096:biosynthesis / Q000235:genetics*; D018626:Retroelements / Q000235:genetics*; D012568:Schizosaccharomyces / Q000235:genetics; D029702:Schizosaccharomyces pombe Proteins / Q000096:biosynthesis / Q000235:genetics*; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D002843:Chromatin; D004268:DNA-Binding Proteins; D018626:Retroelements; D029702:Schizosaccharomyces pombe Proteins; C500467:Sre1 protein, S pombe; C083145:Tf2-6 protein, S pombe; D014157:Transcription Factors; C097691:cbp1 protein, S pombe; C543473:hip1 protein, S pombe; D011495:Histone-Lysine N-Methyltransferase; C472830:Set1 protein, S pombe
keywords: Schizosaccharomyces pombe; Tf2 LTR retrotransposons; higher-order chromatin organization; retrotransposition; transcriptional silencing