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PMID: 29440389 Published · epublish English Journal Article Research Support, Non-U.S. Gov't

Antisense transcription-dependent chromatin signature modulates sense transcript dynamics.

Molecular systems biology ·Vol. 14 ·No. 2 ·2018-00-12 ·Pages e8007

Brown T, Howe FS, Murray SC, Wouters M, Lorenz P, Seward E, Rata S, Angel A, Mellor J

Abstract

Antisense transcription is widespread in genomes. Despite large differences in gene size and architecture, we find that yeast and human genes share a unique, antisense transcription-associated chromatin signature. We asked whether this signature is related to a biological function for antisense transcription. Using quantitative RNA-FISH, we observed changes in sense transcript distributions in nuclei and cytoplasm as antisense transcript levels were altered. To determine the mechanistic differences underlying these distributions, we developed a mathematical framework describing transcription from initiation to transcript degradation. At GAL1, high levels of antisense transcription alter sense transcription dynamics, reducing rates of transcript production and processing, while increasing transcript stability. This relationship with transcript stability is also observed as a genome-wide association. Establishing the antisense transcription-associated chromatin signature through disruption of the Set3C histone deacetylase activity is sufficient to similarly change these rates even in the absence of antisense transcription. Thus, antisense transcription alters sense transcription dynamics in a chromatin-dependent manner.

Keywords
Set3C lysine deacetylase antisense transcription chromatin sense transcript dynamics stochastic model
MeSH Terms
Chromatin/genetics Cytoplasm/genetics Galactokinase/genetics Gene Expression Regulation, Fungal Histone Deacetylases/metabolism Humans In Situ Hybridization, Fluorescence RNA Stability RNA, Antisense/genetics RNA, Fungal/genetics RNA, Messenger/chemistry,genetics Saccharomyces cerevisiae/genetics,metabolism Saccharomyces cerevisiae Proteins/genetics,metabolism Transcription, Genetic
Chemicals
Chromatin RNA, Antisense RNA, Fungal RNA, Messenger Saccharomyces cerevisiae Proteins GAL1 protein, S cerevisiae Galactokinase Set3 protein, S cerevisiae Histone Deacetylases
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Brown Thomas ORCID
Department of Biochemistry, University of Oxford, Oxford, UK.
Howe Françoise S
Department of Biochemistry, University of Oxford, Oxford, UK.
Murray Struan C
Department of Biochemistry, University of Oxford, Oxford, UK.
Wouters Meredith
Department of Biochemistry, University of Oxford, Oxford, UK.
Lorenz Philipp ORCID
Department of Biochemistry, University of Oxford, Oxford, UK.
Seward Emily ORCID
Department of Biochemistry, University of Oxford, Oxford, UK.
Rata Scott
Department of Biochemistry, University of Oxford, Oxford, UK.
Angel Andrew ORCID
Department of Biochemistry, University of Oxford, Oxford, UK andrew.angel@bioch.ox.ac.uk jane.mellor@bioch.ox.ac.uk.
Mellor Jane ORCID
Department of Biochemistry, University of Oxford, Oxford, UK andrew.angel@bioch.ox.ac.uk jane.mellor@bioch.ox.ac.uk.
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Article Info
Journal
Molecular systems biology
Abbr.
Mol Syst Biol
ISSN
1744-4292
Published
2018-00-12
Epub
2018-00-12
Pages
e8007
Language
English
Region
England
NLM ID
101235389
PMCID
PMC5810148
Subset
IM
Grants
Wellcome Trust · WT089156MA · United Kingdom
Biotechnology and Biological Sciences Research Council · BB/P00296X/1 · United Kingdom
Wellcome Trust · 091911 · United Kingdom
Biotechnology and Biological Sciences Research Council · BB/J014427/1 · United Kingdom
Biotechnology and Biological Sciences Research Council · BB/M011224/1 · United Kingdom
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