The Hda1 histone deacetylase limits divergent non-coding transcription and restricts transcription initiation frequency.


Journal

The EMBO journal
ISSN: 1460-2075
Titre abrégé: EMBO J
Pays: England
ID NLM: 8208664

Informations de publication

Date de publication:
01 12 2021
Historique:
revised: 31 08 2021
received: 07 06 2021
accepted: 28 09 2021
pubmed: 19 10 2021
medline: 22 12 2021
entrez: 18 10 2021
Statut: ppublish

Résumé

Nucleosome-depleted regions (NDRs) at gene promoters support initiation of RNA polymerase II transcription. Interestingly, transcription often initiates in both directions, resulting in an mRNA and a divergent non-coding (DNC) transcript of unclear purpose. Here, we characterized the genetic architecture and molecular mechanism of DNC transcription in budding yeast. Using high-throughput reverse genetic screens based on quantitative single-cell fluorescence measurements, we identified the Hda1 histone deacetylase complex (Hda1C) as a repressor of DNC transcription. Nascent transcription profiling showed a genome-wide role of Hda1C in repression of DNC transcription. Live-cell imaging of transcription revealed that mutations in the Hda3 subunit increased the frequency of DNC transcription. Hda1C contributed to decreased acetylation of histone H3 in DNC transcription regions, supporting DNC transcription repression by histone deacetylation. Our data support the interpretation that DNC transcription results as a consequence of the NDR-based architecture of eukaryotic promoters, but that it is governed by locus-specific repression to maintain genome fidelity.

Identifiants

pubmed: 34661296
doi: 10.15252/embj.2021108903
pmc: PMC8634119
doi:

Substances chimiques

Histones 0
Nucleosomes 0
RNA, Untranslated 0
Saccharomyces cerevisiae Proteins 0
RNA Polymerase II EC 2.7.7.-
HDA1 protein, S cerevisiae EC 3.5.1.-
Histone Deacetylases EC 3.5.1.98

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

e108903

Informations de copyright

© 2021 The Authors. Published under the terms of the CC BY NC ND 4.0 license.

Références

BMC Bioinformatics. 2009 Apr 09;10:106
pubmed: 19358741
Science. 2007 Jun 8;316(5830):1484-8
pubmed: 17510325
Trends Biochem Sci. 2020 Dec;45(12):1009-1021
pubmed: 32863101
Science. 2012 Nov 2;338(6107):671-5
pubmed: 23019609
Methods Enzymol. 2010;470:145-79
pubmed: 20946810
EMBO J. 2019 Jun 17;38(12):
pubmed: 31101674
EMBO J. 2021 Dec 1;40(23):e108903
pubmed: 34661296
Nat Protoc. 2007;2(1):31-4
pubmed: 17401334
Mol Cell. 2013 Nov 21;52(4):473-84
pubmed: 24267449
STAR Protoc. 2020 Oct 17;1(3):100142
pubmed: 33377036
Yeast. 1998 Jul;14(10):943-51
pubmed: 9717240
Elife. 2018 Mar 05;7:
pubmed: 29504936
Nat Struct Mol Biol. 2008 Dec;15(12):1263-71
pubmed: 19011635
Nat Rev Genet. 2016 Jan;17(1):47-62
pubmed: 26666209
Nature. 2009 Feb 19;457(7232):1033-7
pubmed: 19169243
Proc Natl Acad Sci U S A. 2013 Feb 19;110(8):2876-81
pubmed: 23382218
Mol Syst Biol. 2011 Feb 15;7:468
pubmed: 21326235
Nat Commun. 2019 Sep 19;10(1):4270
pubmed: 31537788
J Biol Chem. 1996 Jun 28;271(26):15837-44
pubmed: 8663039
Genome Res. 2007 May;17(5):556-65
pubmed: 17387145
Nat Genet. 2014 Dec;46(12):1311-20
pubmed: 25383968
Cell Rep. 2019 Jan 29;26(5):1174-1188.e5
pubmed: 30699347
Mol Cell. 2017 Oct 5;68(1):130-143.e5
pubmed: 28918903
Genes Dev. 2014 Nov 1;28(21):2348-60
pubmed: 25367034
Nat Rev Genet. 2020 Feb;21(2):102-117
pubmed: 31729473
Sci Adv. 2021 Jan 8;7(2):
pubmed: 33523989
Cell. 2001 Mar 23;104(6):817-27
pubmed: 11290320
Nat Struct Mol Biol. 2013 Aug;20(8):923-8
pubmed: 23851456
Cell Rep. 2015 Nov 24;13(8):1610-22
pubmed: 26586442
Nature. 2009 Feb 19;457(7232):1038-42
pubmed: 19169244
Mol Cell. 2018 Dec 20;72(6):955-969.e7
pubmed: 30576657
Science. 2008 Dec 19;322(5909):1845-8
pubmed: 19056941
Cell. 2008 Sep 19;134(6):1066-78
pubmed: 18805098
Proc Natl Acad Sci U S A. 2001 Apr 10;98(8):4391-6
pubmed: 11287668
Nat Struct Mol Biol. 2019 Aug;26(8):744-754
pubmed: 31384063
Proc Natl Acad Sci U S A. 2012 Oct 23;109(43):17454-9
pubmed: 23064634
Science. 2011 Apr 22;332(6028):475-8
pubmed: 21512033
Essays Biochem. 2019 Apr 23;63(1):97-107
pubmed: 30940741
Nat Rev Mol Cell Biol. 2003 Apr;4(4):276-84
pubmed: 12671650
Exp Mol Med. 2020 Feb;52(2):204-212
pubmed: 32071378
Mol Cell. 2012 Feb 24;45(4):470-82
pubmed: 22264825
Annu Rev Biochem. 2020 Jun 20;89:189-212
pubmed: 32208766
Methods. 2006 Dec;40(4):344-52
pubmed: 17101447
Mol Cell. 2015 Nov 19;60(4):597-610
pubmed: 26549684
Nature. 2007 Dec 13;450(7172):1031-5
pubmed: 18075583
PLoS Comput Biol. 2017 Jun 30;13(6):e1005585
pubmed: 28665997
BMC Bioinformatics. 2021 May 31;22(1):290
pubmed: 34058980
Nat Commun. 2018 Feb 22;9(1):780
pubmed: 29472539
Nat Methods. 2013 Feb;10(2):119-21
pubmed: 23263691
Nature. 2011 Jun 22;475(7354):114-7
pubmed: 21697827
Nature. 2012 Jan 18;483(7389):295-301
pubmed: 22258509
Nat Struct Mol Biol. 2007 Feb;14(2):103-5
pubmed: 17277804
Nature. 2013 Jul 18;499(7458):360-3
pubmed: 23792564
Science. 1999 Aug 6;285(5429):901-6
pubmed: 10436161
Mol Cell. 2018 Dec 20;72(6):942-954.e7
pubmed: 30576656
J Mol Biol. 2009 Aug 28;391(4):744-57
pubmed: 19573535
Annu Rev Cell Dev Biol. 2020 Oct 6;36:1-34
pubmed: 32822539
Methods. 2001 Dec;25(4):402-8
pubmed: 11846609
Proc Natl Acad Sci U S A. 2006 Apr 4;103(14):5320-5
pubmed: 16569694
Cell. 2014 Jun 19;157(7):1712-23
pubmed: 24949978
Yeast. 1999 Oct;15(14):1541-53
pubmed: 10514571
Proc Natl Acad Sci U S A. 2018 Jul 3;115(27):7153-7158
pubmed: 29915087
Science. 2008 Dec 19;322(5909):1849-51
pubmed: 19056940
Nature. 2011 Jan 20;469(7330):368-73
pubmed: 21248844
Nucleic Acids Res. 2020 Mar 18;48(5):2332-2347
pubmed: 31863587
BMC Bioinformatics. 2009 Jan 30;10 Suppl 1:S29
pubmed: 19208129
Proc Natl Acad Sci U S A. 2002 Oct 1;99(20):12795-800
pubmed: 12237400
Nat Methods. 2009 May;6(5):343-5
pubmed: 19363495
Cell. 2005 Jun 3;121(5):725-37
pubmed: 15935759
Cell. 2013 Nov 21;155(5):1075-87
pubmed: 24210918
Curr Protoc Mol Biol. 2016;113:14.24.1-14.24.15
pubmed: 27110320

Auteurs

Uthra Gowthaman (U)

Copenhagen Plant Science Centre, Department of Plant and Environmental Sciences, University of Copenhagen, Frederiksberg C, Denmark.

Maxim Ivanov (M)

Copenhagen Plant Science Centre, Department of Plant and Environmental Sciences, University of Copenhagen, Frederiksberg C, Denmark.

Isabel Schwarz (I)

Copenhagen Plant Science Centre, Department of Plant and Environmental Sciences, University of Copenhagen, Frederiksberg C, Denmark.

Heta P Patel (HP)

Division of Gene Regulation, The Netherlands Cancer Institute (NKI), Oncode Institute, Amsterdam, The Netherlands.

Niels A Müller (NA)

Copenhagen Plant Science Centre, Department of Plant and Environmental Sciences, University of Copenhagen, Frederiksberg C, Denmark.

Desiré García-Pichardo (D)

Copenhagen Plant Science Centre, Department of Plant and Environmental Sciences, University of Copenhagen, Frederiksberg C, Denmark.

Tineke L Lenstra (TL)

Division of Gene Regulation, The Netherlands Cancer Institute (NKI), Oncode Institute, Amsterdam, The Netherlands.

Sebastian Marquardt (S)

Copenhagen Plant Science Centre, Department of Plant and Environmental Sciences, University of Copenhagen, Frederiksberg C, Denmark.

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