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Molecular and Cellular Biology, September 2009, p. 5158-5167, Vol. 29, No. 18
0270-7306/09/$08.00+0     doi:10.1128/MCB.00698-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

The Fission Yeast HIRA Histone Chaperone Is Required for Promoter Silencing and the Suppression of Cryptic Antisense Transcripts{triangledown} ,{dagger}

Holly E. Anderson,1,{ddagger} Josephine Wardle,1,{ddagger} Senay Vural Korkut,1,§ Heather E. Murton,1 Luis López-Maury,2 Jürg Bähler,2 and Simon K. Whitehall1*

Institute for Cell & Molecular Biosciences, Newcastle University, Newcastle upon Tyne NE2 4HH, United Kingdom,1 Department of Genetics, Evolution and Environment and UCL Cancer Institute, University College London, London WC1E 6BT, United Kingdom2

Received 29 May 2009/ Returned for modification 22 June 2009/ Accepted 11 July 2009

The assembly of nucleosomes by histone chaperones is an important component of transcriptional regulation. Here, we have assessed the global roles of the HIRA histone chaperone in Schizosaccharomyces pombe. Microarray analysis indicates that inactivation of the HIRA complex results in increased expression of at least 4% of fission yeast genes. HIRA-regulated genes overlap with those which are normally repressed in vegetatively growing cells, such as targets of the Clr6 histone deacetylase and silenced genes located in subtelomeric regions. HIRA is also required for silencing of all 13 intact copies of the Tf2 long terminal repeat (LTR) retrotransposon. However, the role of HIRA is not restricted to bona fide promoters, because HIRA also suppresses noncoding transcripts from solo LTR elements and spurious antisense transcripts from cryptic promoters associated with transcribed regions. Furthermore, the HIRA complex is essential in the absence of the quality control provided by nuclear exosome-mediated degradation of illegitimate transcripts. This suggests that HIRA restricts genomic accessibility, and consistent with this, the chromosomes of cells lacking HIRA are more susceptible to genotoxic agents that cause double-strand breaks. Thus, the HIRA histone chaperone is required to maintain the protective functions of chromatin.


* Corresponding author. Mailing address: Institute for Cell & Molecular Biosciences, Newcastle University, Framlington Place, Newcastle upon Tyne NE2 4HH, United Kingdom. Phone: 44 (0)191 222 5989. Fax: 44 (0)191 222 7424. E-mail: S.K.Whitehall{at}ncl.ac.uk

{triangledown} Published ahead of print on 20 July 2009.

{dagger} Supplemental material for this article may be found at http://mcb.asm.org/.

{ddagger} These authors contributed equally to this study.

§ Present address: Yildiz Technical University, Faculty of Arts and Sciences, Department of Biology, 34210 Esenler/Istanbul, Turkey.


Molecular and Cellular Biology, September 2009, p. 5158-5167, Vol. 29, No. 18
0270-7306/09/$08.00+0     doi:10.1128/MCB.00698-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.