@article{ccf434f0dfff43caab612d148b7eaf17,
title = "Transcription and chromatin-based surveillance mechanism controls suppression of cryptic antisense transcription",
abstract = "Phosphorylation of the RNA polymerase II C-terminal domain Y1S2P3T4S5P6S7 consensus sequence coordinates key events during transcription, and its deregulation leads to defects in transcription and RNA processing. Here, we report that the histone deacetylase activity of the fission yeast Hos2/Set3 complex plays an important role in suppressing cryptic initiation of antisense transcription when RNA polymerase II phosphorylation is dysregulated due to the loss of Ssu72 phosphatase. Interestingly, although single Hos2 and Set3 mutants have little effect, loss of Hos2 or Set3 combined with ssu72Δ results in a synergistic increase in antisense transcription globally and correlates with elevated sensitivity to genotoxic agents. We demonstrate a key role for the Ssu72/Hos2/Set3 mechanism in the suppression of cryptic antisense transcription at the 3′ end of convergent genes that are most susceptible to these defects, ensuring the fidelity of gene expression within dense genomes of simple eukaryotes.",
keywords = "convergent genes, cryptic antisense transcription, histone deacetylase, Hos2/Set3 complex, RNA polymerase II phosphorylation, Ssu72 phosphatase, transcription termination",
author = "Heo, {Dong Hyuk} and Krzysztof Ku{\'s} and Pawel Grzechnik and Tan-Wong, {Sue Mei} and Adrien Birot and Tea Kecman and Soren Nielsen and Nikolay Zenkin and Lidia Vasiljeva",
note = "Funding Information: We thank Naomi Petela, Ewa Chrostek, Caspar Kengeter, and members of the Vasiljeva lab for the critical reading of the manuscript. We thank the National BioResource Yeast Project, Damien Hermand, Beate Schwer, and Matthew Whitby for the yeast strains. This work was supported by a Wellcome Trust Senior Research fellowship to L.V. (WT106994/Z/15/Z), a fellowship from the Korean National Research Foundation (NRF) by the Ministry of Education (2014R1A6A3A03060067) to D.-H.H. Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society to P.G. (200473/Z/16/Z), and Wellcome Trust Investigator Awards to N.Z. (102851/Z/13/Z and 217189/Z/19/Z). D.-H.H. K.K. and L.V. conceived and designed the experiments and wrote the manuscript. D.-H.H. carried out ChIP-seq, ChIP-qPCR, RNA-seq, Northern blot, protein purification, initial bioinformatics analysis, and plate spotting assay. K.K. performed strains construction, protein purifications, and most of the bioinformatics analysis. P.G. performed most of the ChIP-qPCR analysis. A.B. contributed to strain construction and yeast growth assay, T.K. helped with ChIP-seq. S.M.T.-W. performed DRIP and qPCR. S.N. performed the in vitro transcription assay in the N.Z. laboratory. All authors edited the manuscript. The authors declare no competing interests. Funding Information: We thank Naomi Petela, Ewa Chrostek, Caspar Kengeter, and members of the Vasiljeva lab for the critical reading of the manuscript. We thank the National BioResource Yeast Project, Damien Hermand, Beate Schwer, and Matthew Whitby for the yeast strains. This work was supported by a Wellcome Trust Senior Research fellowship to L.V. ( WT106994/Z/15/Z ), a fellowship from the Korean National Research Foundation (NRF) by the Ministry of Education ( 2014R1A6A3A03060067 ) to D.-H.H., Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society to P.G. ( 200473/Z/16/Z ), and Wellcome Trust Investigator Awards to N.Z. ( 102851/Z/13/Z and 217189/Z/19/Z ). Publisher Copyright: {\textcopyright} 2021 The Author(s)",
year = "2021",
month = sep,
day = "7",
doi = "10.1016/j.celrep.2021.109671",
language = "English",
volume = "36",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "10",
}