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: Nicola Zilio, Sandra Codlin, Ajay A Vashisht, Danny A Bitton, Steven R Head, James A Wohlschlegel, Jürg Bähler, Michael N Boddy
• Journal: Molecular and cellular biology (Mol Cell Biol) Vol. 34 Issue 18 Pg. 3500-14 (Sep 15 2014) ISSN: 1098-5549 [Electronic] United States
• PMID: 25002536 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Chemical References

• Cell Cycle Proteins
• Chromatin
• Clr6 protein, S pombe
• RNA, Fungal
• RNA, Long Noncoding
• Schizosaccharomyces pombe Proteins
• Tf2-6 protein, S pombe
• Histone Deacetylases

Topics

• Cell Cycle Proteins (genetics, metabolism)
• Chromatin (genetics, metabolism)
• Chromosomes, Fungal
• Epigenesis, Genetic
• Gene Expression Regulation, Fungal
• Genome, Fungal
• Genomic Instability
• Histone Deacetylases (metabolism)
• Meiosis
• Phenotype
• RNA, Fungal (genetics)
• RNA, Long Noncoding (genetics)
• Schizosaccharomyces (enzymology, genetics, physiology)
• Schizosaccharomyces pombe Proteins (genetics, metabolism)
• Stress, Physiological