Dopamine Signaling Leads to Loss of Polycomb Repression and Aberrant Gene Activation in Experimental Parkinsonism
Identifieur interne : 000325 ( Hal/Corpus ); précédent : 000324; suivant : 000326Dopamine Signaling Leads to Loss of Polycomb Repression and Aberrant Gene Activation in Experimental Parkinsonism
Auteurs : Erik Södersten ; Michael Feyder ; Mads Lerdrup ; Ana-Luisa Gomes ; Hanna Kryh ; Giada Spigolon ; Jocelyne Caboche ; Gilberto Fisone ; Klaus HansenSource :
- PLoS Genetics [ 1553-7390 ] ; 2014-09.
Abstract
Polycomb group (PcG) proteins bind to and repress genes in embryonic stem cells through lineage commitment to the terminal differentiated state. PcG repressed genes are commonly characterized by the presence of the epigenetic histone mark H3K27me3, catalyzed by the Polycomb repressive complex 2. Here, we present in vivo evidence for a previously unrecognized plasticity of PcG-repressed genes in terminally differentiated brain neurons of parkisonian mice. We show that acute administration of the dopamine precursor, L-DOPA, induces a remarkable increase in H3K27me3S28 phosphorylation. The induction of the H3K27me3S28p histone mark specifically occurs in medium spiny neurons expressing dopamine D1 receptors and is dependent on Msk1 kinase activity and DARPP-32-mediated inhibition of protein phosphatase-1. Chromatin immunoprecipitation (ChIP) experiments showed that increased H3K27me3S28p was accompanied by reduced PcG binding to regulatory regions of genes. An analysis of the genome wide distribution of L-DOPA-induced H3K27me3S28 phosphorylation by ChIP sequencing (ChIP-seq) in combination with expression analysis by RNA-sequencing (RNA-seq) showed that the induction of H3K27me3S28p correlated with increased expression of a subset of PcG repressed genes. We found that induction of H3K27me3S28p persisted during chronic L-DOPA administration to parkisonian mice and correlated with aberrant gene expression. We propose that dopaminergic transmission can activate PcG repressed genes in the adult brain and thereby contribute to long-term maladaptive responses including the motor complications, or dyskinesia, caused by prolonged administration of L-DOPA in Parkinson's disease.
Url:
DOI: 10.1371/journal.pgen.1004574
Links to Exploration step
Hal:hal-01342715Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Dopamine Signaling Leads to Loss of Polycomb Repression and Aberrant Gene Activation in Experimental Parkinsonism</title>
<author><name sortKey="Sodersten, Erik" sort="Sodersten, Erik" uniqKey="Sodersten E" first="Erik" last="Södersten">Erik Södersten</name>
<affiliation><hal:affiliation type="institution" xml:id="struct-182755" status="VALID"> <orgName>IT University of Copenhagen</orgName>
<desc> <address> <addrLine>IT University of Copenhagen Rued Langaard Vej 7 Copenhagen, Denmark</addrLine>
<country key="DK"></country>
</address>
<ref type="url">http://en.itu.dk/</ref>
</desc>
</hal:affiliation>
</affiliation>
</author>
<author><name sortKey="Feyder, Michael" sort="Feyder, Michael" uniqKey="Feyder M" first="Michael" last="Feyder">Michael Feyder</name>
<affiliation><hal:affiliation type="institution" xml:id="struct-302344" status="VALID"><orgName>Karolinska Institutet [Stockholm]</orgName>
<desc><address><addrLine>Solnavägen 1, 171 77 SolnaStockholm</addrLine>
<country key="SE"></country>
</address>
<ref type="url">http://ki.se</ref>
</desc>
</hal:affiliation>
</affiliation>
</author>
<author><name sortKey="Lerdrup, Mads" sort="Lerdrup, Mads" uniqKey="Lerdrup M" first="Mads" last="Lerdrup">Mads Lerdrup</name>
<affiliation><hal:affiliation type="institution" xml:id="struct-182755" status="VALID"> <orgName>IT University of Copenhagen</orgName>
<desc> <address> <addrLine>IT University of Copenhagen Rued Langaard Vej 7 Copenhagen, Denmark</addrLine>
<country key="DK"></country>
</address>
<ref type="url">http://en.itu.dk/</ref>
</desc>
</hal:affiliation>
</affiliation>
</author>
<author><name sortKey="Gomes, Ana Luisa" sort="Gomes, Ana Luisa" uniqKey="Gomes A" first="Ana-Luisa" last="Gomes">Ana-Luisa Gomes</name>
<affiliation><hal:affiliation type="institution" xml:id="struct-182755" status="VALID"> <orgName>IT University of Copenhagen</orgName>
<desc> <address> <addrLine>IT University of Copenhagen Rued Langaard Vej 7 Copenhagen, Denmark</addrLine>
<country key="DK"></country>
</address>
<ref type="url">http://en.itu.dk/</ref>
</desc>
</hal:affiliation>
</affiliation>
</author>
<author><name sortKey="Kryh, Hanna" sort="Kryh, Hanna" uniqKey="Kryh H" first="Hanna" last="Kryh">Hanna Kryh</name>
<affiliation><hal:affiliation type="institution" xml:id="struct-182755" status="VALID"> <orgName>IT University of Copenhagen</orgName>
<desc> <address> <addrLine>IT University of Copenhagen Rued Langaard Vej 7 Copenhagen, Denmark</addrLine>
<country key="DK"></country>
</address>
<ref type="url">http://en.itu.dk/</ref>
</desc>
</hal:affiliation>
</affiliation>
</author>
<author><name sortKey="Spigolon, Giada" sort="Spigolon, Giada" uniqKey="Spigolon G" first="Giada" last="Spigolon">Giada Spigolon</name>
<affiliation><hal:affiliation type="institution" xml:id="struct-302344" status="VALID"><orgName>Karolinska Institutet [Stockholm]</orgName>
<desc><address><addrLine>Solnavägen 1, 171 77 SolnaStockholm</addrLine>
<country key="SE"></country>
</address>
<ref type="url">http://ki.se</ref>
</desc>
</hal:affiliation>
</affiliation>
</author>
<author><name sortKey="Caboche, Jocelyne" sort="Caboche, Jocelyne" uniqKey="Caboche J" first="Jocelyne" last="Caboche">Jocelyne Caboche</name>
<affiliation><hal:affiliation type="laboratory" xml:id="struct-81502" status="OLD"> <orgName>Physiopathologie des Maladies du Système Nerveux Central</orgName>
<desc> <address> <addrLine>Bât. B, 4ème étage, case courrier 37 9 quai Saint Bernard 75252 Paris Cedex 05</addrLine>
<country key="FR"></country>
</address>
</desc>
<listRelation> <relation active="#struct-93591" type="direct"></relation>
<relation name="U952" active="#struct-303623" type="direct"></relation>
<relation name="UMR7224" active="#struct-441569" type="direct"></relation>
</listRelation>
<tutelles><tutelle active="#struct-93591" type="direct"><org type="institution" xml:id="struct-93591" status="VALID"> <orgName>Université Pierre et Marie Curie - Paris 6</orgName>
<orgName type="acronym">UPMC</orgName>
<desc> <address> <addrLine>4 place Jussieu - 75005 Paris</addrLine>
<country key="FR"></country>
</address>
<ref type="url">http://www.upmc.fr/</ref>
</desc>
</org>
</tutelle>
<tutelle name="U952" active="#struct-303623" type="direct"><org type="institution" xml:id="struct-303623" status="VALID"> <idno type="IdRef">026388278</idno>
<orgName>Institut National de la Santé et de la Recherche Médicale</orgName>
<orgName type="acronym">INSERM</orgName>
<desc> <address> <addrLine>101, rue de Tolbiac, 75013 Paris </addrLine>
<country key="FR"></country>
</address>
<ref type="url">http://www.inserm.fr</ref>
</desc>
</org>
</tutelle>
<tutelle name="UMR7224" active="#struct-441569" type="direct"><org type="institution" xml:id="struct-441569" status="VALID"> <idno type="IdRef">02636817X</idno>
<idno type="ISNI">0000000122597504</idno>
<orgName>Centre National de la Recherche Scientifique</orgName>
<orgName type="acronym">CNRS</orgName>
<date type="start">1939-10-19</date>
<desc> <address> <country key="FR"></country>
</address>
<ref type="url">http://www.cnrs.fr/</ref>
</desc>
</org>
</tutelle>
</tutelles>
</hal:affiliation>
</affiliation>
</author>
<author><name sortKey="Fisone, Gilberto" sort="Fisone, Gilberto" uniqKey="Fisone G" first="Gilberto" last="Fisone">Gilberto Fisone</name>
<affiliation><hal:affiliation type="institution" xml:id="struct-302344" status="VALID"><orgName>Karolinska Institutet [Stockholm]</orgName>
<desc><address><addrLine>Solnavägen 1, 171 77 SolnaStockholm</addrLine>
<country key="SE"></country>
</address>
<ref type="url">http://ki.se</ref>
</desc>
</hal:affiliation>
</affiliation>
</author>
<author><name sortKey="Hansen, Klaus" sort="Hansen, Klaus" uniqKey="Hansen K" first="Klaus" last="Hansen">Klaus Hansen</name>
<affiliation><hal:affiliation type="institution" xml:id="struct-182755" status="VALID"> <orgName>IT University of Copenhagen</orgName>
<desc> <address> <addrLine>IT University of Copenhagen Rued Langaard Vej 7 Copenhagen, Denmark</addrLine>
<country key="DK"></country>
</address>
<ref type="url">http://en.itu.dk/</ref>
</desc>
</hal:affiliation>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">HAL</idno>
<idno type="RBID">Hal:hal-01342715</idno>
<idno type="halId">hal-01342715</idno>
<idno type="halUri">http://hal.upmc.fr/hal-01342715</idno>
<idno type="url">http://hal.upmc.fr/hal-01342715</idno>
<idno type="doi">10.1371/journal.pgen.1004574</idno>
<date when="2014-09">2014-09</date>
<idno type="wicri:Area/Hal/Corpus">000325</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en">Dopamine Signaling Leads to Loss of Polycomb Repression and Aberrant Gene Activation in Experimental Parkinsonism</title>
<author><name sortKey="Sodersten, Erik" sort="Sodersten, Erik" uniqKey="Sodersten E" first="Erik" last="Södersten">Erik Södersten</name>
<affiliation><hal:affiliation type="institution" xml:id="struct-182755" status="VALID"> <orgName>IT University of Copenhagen</orgName>
<desc> <address> <addrLine>IT University of Copenhagen Rued Langaard Vej 7 Copenhagen, Denmark</addrLine>
<country key="DK"></country>
</address>
<ref type="url">http://en.itu.dk/</ref>
</desc>
</hal:affiliation>
</affiliation>
</author>
<author><name sortKey="Feyder, Michael" sort="Feyder, Michael" uniqKey="Feyder M" first="Michael" last="Feyder">Michael Feyder</name>
<affiliation><hal:affiliation type="institution" xml:id="struct-302344" status="VALID"><orgName>Karolinska Institutet [Stockholm]</orgName>
<desc><address><addrLine>Solnavägen 1, 171 77 SolnaStockholm</addrLine>
<country key="SE"></country>
</address>
<ref type="url">http://ki.se</ref>
</desc>
</hal:affiliation>
</affiliation>
</author>
<author><name sortKey="Lerdrup, Mads" sort="Lerdrup, Mads" uniqKey="Lerdrup M" first="Mads" last="Lerdrup">Mads Lerdrup</name>
<affiliation><hal:affiliation type="institution" xml:id="struct-182755" status="VALID"> <orgName>IT University of Copenhagen</orgName>
<desc> <address> <addrLine>IT University of Copenhagen Rued Langaard Vej 7 Copenhagen, Denmark</addrLine>
<country key="DK"></country>
</address>
<ref type="url">http://en.itu.dk/</ref>
</desc>
</hal:affiliation>
</affiliation>
</author>
<author><name sortKey="Gomes, Ana Luisa" sort="Gomes, Ana Luisa" uniqKey="Gomes A" first="Ana-Luisa" last="Gomes">Ana-Luisa Gomes</name>
<affiliation><hal:affiliation type="institution" xml:id="struct-182755" status="VALID"> <orgName>IT University of Copenhagen</orgName>
<desc> <address> <addrLine>IT University of Copenhagen Rued Langaard Vej 7 Copenhagen, Denmark</addrLine>
<country key="DK"></country>
</address>
<ref type="url">http://en.itu.dk/</ref>
</desc>
</hal:affiliation>
</affiliation>
</author>
<author><name sortKey="Kryh, Hanna" sort="Kryh, Hanna" uniqKey="Kryh H" first="Hanna" last="Kryh">Hanna Kryh</name>
<affiliation><hal:affiliation type="institution" xml:id="struct-182755" status="VALID"> <orgName>IT University of Copenhagen</orgName>
<desc> <address> <addrLine>IT University of Copenhagen Rued Langaard Vej 7 Copenhagen, Denmark</addrLine>
<country key="DK"></country>
</address>
<ref type="url">http://en.itu.dk/</ref>
</desc>
</hal:affiliation>
</affiliation>
</author>
<author><name sortKey="Spigolon, Giada" sort="Spigolon, Giada" uniqKey="Spigolon G" first="Giada" last="Spigolon">Giada Spigolon</name>
<affiliation><hal:affiliation type="institution" xml:id="struct-302344" status="VALID"><orgName>Karolinska Institutet [Stockholm]</orgName>
<desc><address><addrLine>Solnavägen 1, 171 77 SolnaStockholm</addrLine>
<country key="SE"></country>
</address>
<ref type="url">http://ki.se</ref>
</desc>
</hal:affiliation>
</affiliation>
</author>
<author><name sortKey="Caboche, Jocelyne" sort="Caboche, Jocelyne" uniqKey="Caboche J" first="Jocelyne" last="Caboche">Jocelyne Caboche</name>
<affiliation><hal:affiliation type="laboratory" xml:id="struct-81502" status="OLD"> <orgName>Physiopathologie des Maladies du Système Nerveux Central</orgName>
<desc> <address> <addrLine>Bât. B, 4ème étage, case courrier 37 9 quai Saint Bernard 75252 Paris Cedex 05</addrLine>
<country key="FR"></country>
</address>
</desc>
<listRelation> <relation active="#struct-93591" type="direct"></relation>
<relation name="U952" active="#struct-303623" type="direct"></relation>
<relation name="UMR7224" active="#struct-441569" type="direct"></relation>
</listRelation>
<tutelles><tutelle active="#struct-93591" type="direct"><org type="institution" xml:id="struct-93591" status="VALID"> <orgName>Université Pierre et Marie Curie - Paris 6</orgName>
<orgName type="acronym">UPMC</orgName>
<desc> <address> <addrLine>4 place Jussieu - 75005 Paris</addrLine>
<country key="FR"></country>
</address>
<ref type="url">http://www.upmc.fr/</ref>
</desc>
</org>
</tutelle>
<tutelle name="U952" active="#struct-303623" type="direct"><org type="institution" xml:id="struct-303623" status="VALID"> <idno type="IdRef">026388278</idno>
<orgName>Institut National de la Santé et de la Recherche Médicale</orgName>
<orgName type="acronym">INSERM</orgName>
<desc> <address> <addrLine>101, rue de Tolbiac, 75013 Paris </addrLine>
<country key="FR"></country>
</address>
<ref type="url">http://www.inserm.fr</ref>
</desc>
</org>
</tutelle>
<tutelle name="UMR7224" active="#struct-441569" type="direct"><org type="institution" xml:id="struct-441569" status="VALID"> <idno type="IdRef">02636817X</idno>
<idno type="ISNI">0000000122597504</idno>
<orgName>Centre National de la Recherche Scientifique</orgName>
<orgName type="acronym">CNRS</orgName>
<date type="start">1939-10-19</date>
<desc> <address> <country key="FR"></country>
</address>
<ref type="url">http://www.cnrs.fr/</ref>
</desc>
</org>
</tutelle>
</tutelles>
</hal:affiliation>
</affiliation>
</author>
<author><name sortKey="Fisone, Gilberto" sort="Fisone, Gilberto" uniqKey="Fisone G" first="Gilberto" last="Fisone">Gilberto Fisone</name>
<affiliation><hal:affiliation type="institution" xml:id="struct-302344" status="VALID"><orgName>Karolinska Institutet [Stockholm]</orgName>
<desc><address><addrLine>Solnavägen 1, 171 77 SolnaStockholm</addrLine>
<country key="SE"></country>
</address>
<ref type="url">http://ki.se</ref>
</desc>
</hal:affiliation>
</affiliation>
</author>
<author><name sortKey="Hansen, Klaus" sort="Hansen, Klaus" uniqKey="Hansen K" first="Klaus" last="Hansen">Klaus Hansen</name>
<affiliation><hal:affiliation type="institution" xml:id="struct-182755" status="VALID"> <orgName>IT University of Copenhagen</orgName>
<desc> <address> <addrLine>IT University of Copenhagen Rued Langaard Vej 7 Copenhagen, Denmark</addrLine>
<country key="DK"></country>
</address>
<ref type="url">http://en.itu.dk/</ref>
</desc>
</hal:affiliation>
</affiliation>
</author>
</analytic>
<idno type="DOI">10.1371/journal.pgen.1004574</idno>
<series><title level="j">PLoS Genetics</title>
<idno type="ISSN">1553-7390</idno>
<imprint><date type="datePub">2014-09</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass></textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en">Polycomb group (PcG) proteins bind to and repress genes in embryonic stem cells through lineage commitment to the terminal differentiated state. PcG repressed genes are commonly characterized by the presence of the epigenetic histone mark H3K27me3, catalyzed by the Polycomb repressive complex 2. Here, we present in vivo evidence for a previously unrecognized plasticity of PcG-repressed genes in terminally differentiated brain neurons of parkisonian mice. We show that acute administration of the dopamine precursor, L-DOPA, induces a remarkable increase in H3K27me3S28 phosphorylation. The induction of the H3K27me3S28p histone mark specifically occurs in medium spiny neurons expressing dopamine D1 receptors and is dependent on Msk1 kinase activity and DARPP-32-mediated inhibition of protein phosphatase-1. Chromatin immunoprecipitation (ChIP) experiments showed that increased H3K27me3S28p was accompanied by reduced PcG binding to regulatory regions of genes. An analysis of the genome wide distribution of L-DOPA-induced H3K27me3S28 phosphorylation by ChIP sequencing (ChIP-seq) in combination with expression analysis by RNA-sequencing (RNA-seq) showed that the induction of H3K27me3S28p correlated with increased expression of a subset of PcG repressed genes. We found that induction of H3K27me3S28p persisted during chronic L-DOPA administration to parkisonian mice and correlated with aberrant gene expression. We propose that dopaminergic transmission can activate PcG repressed genes in the adult brain and thereby contribute to long-term maladaptive responses including the motor complications, or dyskinesia, caused by prolonged administration of L-DOPA in Parkinson's disease.</div>
</front>
</TEI>
<hal api="V3"> <titleStmt> <title xml:lang="en">Dopamine Signaling Leads to Loss of Polycomb Repression and Aberrant Gene Activation in Experimental Parkinsonism</title>
<author role="aut"> <persName> <forename type="first">Erik</forename>
<surname>Södersten</surname>
</persName>
<idno type="halauthorid">1361407</idno>
<affiliation ref="#struct-182755"></affiliation>
<affiliation ref="#struct-302344"></affiliation>
</author>
<author role="aut"> <persName> <forename type="first">Michael</forename>
<surname>Feyder</surname>
</persName>
<idno type="halauthorid">1169179</idno>
<affiliation ref="#struct-302344"></affiliation>
</author>
<author role="aut"> <persName> <forename type="first">Mads</forename>
<surname>Lerdrup</surname>
</persName>
<idno type="halauthorid">1361408</idno>
<affiliation ref="#struct-182755"></affiliation>
</author>
<author role="aut"> <persName> <forename type="first">Ana-Luisa</forename>
<surname>Gomes</surname>
</persName>
<idno type="halauthorid">1361409</idno>
<affiliation ref="#struct-182755"></affiliation>
</author>
<author role="aut"> <persName> <forename type="first">Hanna</forename>
<surname>Kryh</surname>
</persName>
<idno type="halauthorid">1361410</idno>
<affiliation ref="#struct-182755"></affiliation>
</author>
<author role="aut"> <persName> <forename type="first">Giada</forename>
<surname>Spigolon</surname>
</persName>
<idno type="halauthorid">1361411</idno>
<affiliation ref="#struct-302344"></affiliation>
</author>
<author role="aut"> <persName> <forename type="first">Jocelyne</forename>
<surname>Caboche</surname>
</persName>
<idno type="halauthorid">161870</idno>
<affiliation ref="#struct-81502"></affiliation>
</author>
<author role="aut"> <persName> <forename type="first">Gilberto</forename>
<surname>Fisone</surname>
</persName>
<idno type="halauthorid">224336</idno>
<affiliation ref="#struct-302344"></affiliation>
</author>
<author role="aut"> <persName> <forename type="first">Klaus</forename>
<surname>Hansen</surname>
</persName>
<idno type="halauthorid">1361412</idno>
<affiliation ref="#struct-182755"></affiliation>
</author>
<editor role="depositor"> <persName> <forename>Gestionnaire</forename>
<surname>HAL-UPMC</surname>
</persName>
<email type="md5">6d9ad2d5331d206e4ad27346e79eb6c9</email>
<email type="domain">upmc.fr</email>
</editor>
</titleStmt>
<editionStmt> <edition n="v1" type="current"> <date type="whenSubmitted">2016-07-06 15:31:11</date>
<date type="whenModified">2016-07-12 09:53:12</date>
<date type="whenReleased">2016-07-11 09:48:40</date>
<date type="whenProduced">2014-09</date>
<date type="whenEndEmbargoed">2016-07-06</date>
<ref type="file" target="http://hal.upmc.fr/hal-01342715/document"> <date notBefore="2016-07-06"></date>
</ref>
<ref type="file" subtype="publisherPaid" n="1" target="http://hal.upmc.fr/hal-01342715/file/journal.pgen.1004574.PDF"> <date notBefore="2016-07-06"></date>
</ref>
</edition>
<respStmt> <resp>contributor</resp>
<name key="320715"> <persName> <forename>Gestionnaire</forename>
<surname>HAL-UPMC</surname>
</persName>
<email type="md5">6d9ad2d5331d206e4ad27346e79eb6c9</email>
<email type="domain">upmc.fr</email>
</name>
</respStmt>
</editionStmt>
<publicationStmt> <distributor>CCSD</distributor>
<idno type="halId">hal-01342715</idno>
<idno type="halUri">http://hal.upmc.fr/hal-01342715</idno>
<idno type="halBibtex">sodersten:hal-01342715</idno>
<idno type="halRefHtml">PLoS Genetics, Public Library of Science, 2014, 10 (9), pp.e1004574. <10.1371/journal.pgen.1004574></idno>
<idno type="halRef">PLoS Genetics, Public Library of Science, 2014, 10 (9), pp.e1004574. <10.1371/journal.pgen.1004574></idno>
<availability status="restricted"> <licence target="http://creativecommons.org/licenses/by/">Attribution</licence>
</availability>
</publicationStmt>
<seriesStmt> <idno type="stamp" n="UPMC">Université Pierre et Marie Curie</idno>
<idno type="stamp" n="CNRS">CNRS - Centre national de la recherche scientifique</idno>
<idno type="stamp" n="PMSNC">U952 - Physiopathologie des Maladies du Système Nerveux Central</idno>
<idno type="stamp" n="INSERM">INSERM - Institut national de la santé et de la recherche médicale</idno>
</seriesStmt>
<notesStmt> <note type="audience" n="2">International</note>
<note type="popular" n="0">No</note>
<note type="peer" n="1">Yes</note>
</notesStmt>
<sourceDesc> <biblStruct> <analytic> <title xml:lang="en">Dopamine Signaling Leads to Loss of Polycomb Repression and Aberrant Gene Activation in Experimental Parkinsonism</title>
<author role="aut"> <persName> <forename type="first">Erik</forename>
<surname>Södersten</surname>
</persName>
<idno type="halauthorid">1361407</idno>
<affiliation ref="#struct-182755"></affiliation>
<affiliation ref="#struct-302344"></affiliation>
</author>
<author role="aut"> <persName> <forename type="first">Michael</forename>
<surname>Feyder</surname>
</persName>
<idno type="halauthorid">1169179</idno>
<affiliation ref="#struct-302344"></affiliation>
</author>
<author role="aut"> <persName> <forename type="first">Mads</forename>
<surname>Lerdrup</surname>
</persName>
<idno type="halauthorid">1361408</idno>
<affiliation ref="#struct-182755"></affiliation>
</author>
<author role="aut"> <persName> <forename type="first">Ana-Luisa</forename>
<surname>Gomes</surname>
</persName>
<idno type="halauthorid">1361409</idno>
<affiliation ref="#struct-182755"></affiliation>
</author>
<author role="aut"> <persName> <forename type="first">Hanna</forename>
<surname>Kryh</surname>
</persName>
<idno type="halauthorid">1361410</idno>
<affiliation ref="#struct-182755"></affiliation>
</author>
<author role="aut"> <persName> <forename type="first">Giada</forename>
<surname>Spigolon</surname>
</persName>
<idno type="halauthorid">1361411</idno>
<affiliation ref="#struct-302344"></affiliation>
</author>
<author role="aut"> <persName> <forename type="first">Jocelyne</forename>
<surname>Caboche</surname>
</persName>
<idno type="halauthorid">161870</idno>
<affiliation ref="#struct-81502"></affiliation>
</author>
<author role="aut"> <persName> <forename type="first">Gilberto</forename>
<surname>Fisone</surname>
</persName>
<idno type="halauthorid">224336</idno>
<affiliation ref="#struct-302344"></affiliation>
</author>
<author role="aut"> <persName> <forename type="first">Klaus</forename>
<surname>Hansen</surname>
</persName>
<idno type="halauthorid">1361412</idno>
<affiliation ref="#struct-182755"></affiliation>
</author>
</analytic>
<monogr> <idno type="halJournalId" status="VALID">1957</idno>
<idno type="issn">1553-7390</idno>
<idno type="eissn">1553-7404</idno>
<title level="j">PLoS Genetics</title>
<imprint> <publisher>Public Library of Science</publisher>
<biblScope unit="volume">10</biblScope>
<biblScope unit="issue">9</biblScope>
<biblScope unit="pp">e1004574</biblScope>
<date type="datePub">2014-09</date>
</imprint>
</monogr>
<idno type="doi">10.1371/journal.pgen.1004574</idno>
</biblStruct>
</sourceDesc>
<profileDesc> <langUsage> <language ident="en">English</language>
</langUsage>
<textClass> <classCode scheme="halDomain" n="sdv.gen">Life Sciences [q-bio]/Genetics</classCode>
<classCode scheme="halTypology" n="ART">Journal articles</classCode>
</textClass>
<abstract xml:lang="en">Polycomb group (PcG) proteins bind to and repress genes in embryonic stem cells through lineage commitment to the terminal differentiated state. PcG repressed genes are commonly characterized by the presence of the epigenetic histone mark H3K27me3, catalyzed by the Polycomb repressive complex 2. Here, we present in vivo evidence for a previously unrecognized plasticity of PcG-repressed genes in terminally differentiated brain neurons of parkisonian mice. We show that acute administration of the dopamine precursor, L-DOPA, induces a remarkable increase in H3K27me3S28 phosphorylation. The induction of the H3K27me3S28p histone mark specifically occurs in medium spiny neurons expressing dopamine D1 receptors and is dependent on Msk1 kinase activity and DARPP-32-mediated inhibition of protein phosphatase-1. Chromatin immunoprecipitation (ChIP) experiments showed that increased H3K27me3S28p was accompanied by reduced PcG binding to regulatory regions of genes. An analysis of the genome wide distribution of L-DOPA-induced H3K27me3S28 phosphorylation by ChIP sequencing (ChIP-seq) in combination with expression analysis by RNA-sequencing (RNA-seq) showed that the induction of H3K27me3S28p correlated with increased expression of a subset of PcG repressed genes. We found that induction of H3K27me3S28p persisted during chronic L-DOPA administration to parkisonian mice and correlated with aberrant gene expression. We propose that dopaminergic transmission can activate PcG repressed genes in the adult brain and thereby contribute to long-term maladaptive responses including the motor complications, or dyskinesia, caused by prolonged administration of L-DOPA in Parkinson's disease.</abstract>
</profileDesc>
</hal>
</record>
Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Sante/explor/ParkinsonFranceV1/Data/Hal/Corpus
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000325 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Hal/Corpus/biblio.hfd -nk 000325 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien |wiki= Wicri/Sante |area= ParkinsonFranceV1 |flux= Hal |étape= Corpus |type= RBID |clé= Hal:hal-01342715 |texte= Dopamine Signaling Leads to Loss of Polycomb Repression and Aberrant Gene Activation in Experimental Parkinsonism }}
![]() | This area was generated with Dilib version V0.6.29. | ![]() |