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PMID: 24497191 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Role of histone modifications and early termination in pervasive transcription and antisense-mediated gene silencing in yeast.

Nucleic acids research ·Vol. 42 ·No. 7 ·2014-04-00 ·Pages 4348-62

Castelnuovo M, Zaugg JB, Guffanti E, Maffioletti A, Camblong J, Xu Z, Clauder-Münster S, Steinmetz LM, Luscombe NM, Stutz F

Abstract

Most genomes, including yeast Saccharomyces cerevisiae, are pervasively transcribed producing numerous non-coding RNAs, many of which are unstable and eliminated by nuclear or cytoplasmic surveillance pathways. We previously showed that accumulation of PHO84 antisense RNA (asRNA), in cells lacking the nuclear exosome component Rrp6, is paralleled by repression of sense transcription in a process dependent on the Hda1 histone deacetylase (HDAC) and the H3K4 histone methyl transferase Set1. Here we investigate this process genome-wide and measure the whole transcriptome of various histone modification mutants in a Δrrp6 strain using tiling arrays. We confirm widespread occurrence of potentially antisense-dependent gene regulation and identify three functionally distinct classes of genes that accumulate asRNAs in the absence of Rrp6. These classes differ in whether the genes are silenced by the asRNA and whether the silencing is HDACs and histone methyl transferase-dependent. Among the distinguishing features of asRNAs with regulatory potential, we identify weak early termination by Nrd1/Nab3/Sen1, extension of the asRNA into the open reading frame promoter and dependence of the silencing capacity on Set1 and the HDACs Hda1 and Rpd3 particularly at promoters undergoing extensive chromatin remodelling. Finally, depending on the efficiency of Nrd1/Nab3/Sen1 early termination, asRNA levels are modulated and their capability of silencing is changed.

MeSH Terms
Gene Expression Regulation, Fungal Gene Silencing Histone-Lysine N-Methyltransferase/physiology Histones/metabolism Proton-Phosphate Symporters/genetics RNA, Antisense/biosynthesis,metabolism RNA-Binding Proteins/metabolism Saccharomyces cerevisiae/genetics,metabolism Saccharomyces cerevisiae Proteins/genetics,metabolism,physiology Transcription Termination, Genetic
Chemicals
Histones PHO84 protein, S cerevisiae Proton-Phosphate Symporters RNA, Antisense RNA-Binding Proteins Saccharomyces cerevisiae Proteins Histone-Lysine N-Methyltransferase SET1 protein, S cerevisiae
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Castelnuovo Manuele
Department of Cell Biology and NCCR "Frontiers in Genetics", iGE3, University of Geneva, 1211 Geneva, Switzerland, EBI-EMBL Hinxton, Cambridge CB101SD, England, European Molecular Biology Laboratory, 69117 Heidelberg, Germany, Department of Genetics, Stanford University, Stanford, CA 94395 USA and Stanford Genome Technology Center, Palo Alto, CA 94303, USA.
Zaugg Judith B
Guffanti Elisa
Maffioletti Andrea
Camblong Jurgi
Xu Zhenyu
Clauder-Münster Sandra
Steinmetz Lars M
Luscombe Nicholas M
Stutz Françoise
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Article Info
Journal
Nucleic acids research
Abbr.
Nucleic Acids Res
ISSN
1362-4962
DOI
10.1093/nar/gku100
Published
2014-04-00
Epub
2014-00-04
Pages
4348-62
Language
English
Region
England
NLM ID
0411011
PMCID
PMC3985671
Subset
IM
Grants
NHGRI NIH HHS · P01 HG000205 · United States
NIGMS NIH HHS · R01 GM068717 · United States
External Links
PubMed source DOI: 10.1093/nar/gku100 PMC Full Text View journal details
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