title: A novel histone deacetylase complex in the control of transcription and genome stability.
abstract: The acetylation state of histones, controlled by histone acetyltransferases (HATs) and deacetylases (HDACs), profoundly affects DNA transcription and repair by modulating chromatin accessibility to the cellular machinery. The Schizosaccharomyces pombe HDAC Clr6 (human HDAC1) binds to different sets of proteins that define functionally distinct complexes: I, I', and II. Here, we determine the composition, architecture, and functions of a new Clr6 HDAC complex, I'', delineated by the novel proteins Nts1, Mug165, and Png3. Deletion of nts1 causes increased sensitivity to genotoxins and deregulated expression of Tf2 elements, long noncoding RNA, and subtelomeric and stress-related genes. Similar, but more pervasive, phenotypes are observed upon Clr6 inactivation, supporting the designation of complex I'' as a mediator of a key subset of Clr6 functions. We also reveal that with the exception of Tf2 elements, the genome-wide loading sites and loci regulated by Clr6 I″ do not correlate. Instead, Nts1 loads at genes that are expressed in midmeiosis, following oxidative stress, or are periodically expressed. Collective data suggest that Clr6 I'' has (i) indirect effects on gene expression, conceivably by mediating higher-order chromatin organization of subtelomeres and Tf2 elements, and (ii) direct effects on the transcription of specific genes in response to certain cellular or environmental stimuli.
authors.affiliation: Department of Cell and Molecular Biology, The Scripps Research Institute, La Jolla, California, USA.
authors.forename: Nicola
authors.initials: N
authors.lastname: Zilio
authors.affiliation: University College London, Department of Genetics, Evolution & Environment, and UCL Cancer Institute, London, United Kingdom.
authors.forename: Sandra
authors.initials: S
authors.lastname: Codlin
authors.affiliation: Department of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles, California, USA.
authors.forename: Ajay A
authors.initials: AA
authors.lastname: Vashisht
authors.affiliation: University College London, Department of Genetics, Evolution & Environment, and UCL Cancer Institute, London, United Kingdom.
authors.forename: Danny A
authors.initials: DA
authors.lastname: Bitton
authors.affiliation: Next Generation Sequencing Core, The Scripps Research Institute, La Jolla, California, USA.
authors.forename: Steven R
authors.initials: SR
authors.lastname: Head
authors.affiliation: Department of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles, California, USA.
authors.forename: James A
authors.initials: JA
authors.lastname: Wohlschlegel
authors.affiliation: University College London, Department of Genetics, Evolution & Environment, and UCL Cancer Institute, London, United Kingdom.
authors.forename: Jürg
authors.initials: J
authors.lastname: Bähler
authors.affiliation: Department of Cell and Molecular Biology, The Scripps Research Institute, La Jolla, California, USA nboddy@scripps.edu.
authors.forename: Michael N
authors.initials: MN
authors.lastname: Boddy
mesh_terms: D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002843:Chromatin / Q000235:genetics / Q000378:metabolism; D015825:Chromosomes, Fungal; D044127:Epigenesis, Genetic; D015966:Gene Expression Regulation, Fungal; D016681:Genome, Fungal; D042822:Genomic Instability; D006655:Histone Deacetylases / Q000378:metabolism*; D008540:Meiosis; D010641:Phenotype; D012331:RNA, Fungal / Q000235:genetics; D062085:RNA, Long Noncoding / Q000235:genetics; D012568:Schizosaccharomyces / Q000201:enzymology* / Q000235:genetics / Q000502:physiology; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics* / Q000378:metabolism*; D013312:Stress, Physiological
chemical_list: D018797:Cell Cycle Proteins; D002843:Chromatin; C115303:Clr6 protein, S pombe; D012331:RNA, Fungal; D062085:RNA, Long Noncoding; D029702:Schizosaccharomyces pombe Proteins; C083145:Tf2-6 protein, S pombe; D006655:Histone Deacetylases