A novel isoform of the orphan nuclear receptor ROR β is specifically expressed in pineal gland and retina
Identifieur interne : 000538 ( Main/Corpus ); précédent : 000537; suivant : 000539A novel isoform of the orphan nuclear receptor ROR β is specifically expressed in pineal gland and retina
Auteurs : Elisabeth André ; Katrin Gawlas ; Markus Steinmayr ; Michael Becker-AndréSource :
- Gene [ 0378-1119 ] ; 1998.
Abstract
RORβ is a member of the nuclear hormone receptor superfamily whose ligand is unknown. Expression of RORβ is confined to the central nervous system and its pattern suggests that this orphan nuclear receptor is implicated in the processing of sensory information and in circadian timing. In rats, RORβ mRNA levels oscillate robustly in pineal gland and retina, displaying a 24h rhythm. Here we report the cloning of the cDNA of a novel isoform of RORβ from rat pineal tissue. Expression of this isoform, called RORβ2, is confined to pineal gland and retina and strongly increases at night. RORβ2 shares common DNA- and putative ligand-binding domains with the canonical RORβ (referred to as RORβ1), but is characterized by a different amino-terminal domain. This structural difference renders RORβ2 much more selectively binding to DNA than RORβ1. Moreover, in contrast to RORβ1, the novel isoform efficiently activates transcription also in non-neuronal cell lines. Thus, the two RORβ isoforms are likely to regulate different sets of genes in different physiological contexts.
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DOI: 10.1016/S0378-1119(98)00348-5
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<record><TEI wicri:istexFullTextTei="biblStruct"><teiHeader><fileDesc><titleStmt><title>A novel isoform of the orphan nuclear receptor ROR β is specifically expressed in pineal gland and retina</title><author><name sortKey="Andre, Elisabeth" sort="Andre, Elisabeth" uniqKey="Andre E" first="Elisabeth" last="André">Elisabeth André</name><affiliation><mods:affiliation>Serono Pharmaceutical Research Institute S.A., 14, chemin des Aulx, CH-1228 Plan-les-Ouates, Switzerland</mods:affiliation></affiliation></author><author><name sortKey="Gawlas, Katrin" sort="Gawlas, Katrin" uniqKey="Gawlas K" first="Katrin" last="Gawlas">Katrin Gawlas</name><affiliation><mods:affiliation>University of Nijmegen, Toernooiveld 1, NL-6525 ED Neijmegen, The Netherlands</mods:affiliation></affiliation></author><author><name sortKey="Steinmayr, Markus" sort="Steinmayr, Markus" uniqKey="Steinmayr M" first="Markus" last="Steinmayr">Markus Steinmayr</name><affiliation><mods:affiliation>Schering AG, Heinrich Heine Str. 20, D-10179 Berlin, Germany</mods:affiliation></affiliation></author><author><name sortKey="Becker Andre, Michael" sort="Becker Andre, Michael" uniqKey="Becker Andre M" first="Michael" last="Becker-André">Michael Becker-André</name><affiliation><mods:affiliation>Serono Pharmaceutical Research Institute S.A., 14, chemin des Aulx, CH-1228 Plan-les-Ouates, Switzerland</mods:affiliation></affiliation><affiliation><mods:affiliation>Corresponding author. Tel: +41-22-7069-737; Fax: +41-22-794.69.65; e-mail: michael.becker-andre@serono.com</mods:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:A22D25BEBAE94025B2269BAB785D496C150DD876</idno><date when="1998" year="1998">1998</date><idno type="doi">10.1016/S0378-1119(98)00348-5</idno><idno type="url">https://api.istex.fr/document/A22D25BEBAE94025B2269BAB785D496C150DD876/fulltext/pdf</idno><idno type="wicri:Area/Main/Corpus">000538</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a">A novel isoform of the orphan nuclear receptor ROR β is specifically expressed in pineal gland and retina</title><author><name sortKey="Andre, Elisabeth" sort="Andre, Elisabeth" uniqKey="Andre E" first="Elisabeth" last="André">Elisabeth André</name><affiliation><mods:affiliation>Serono Pharmaceutical Research Institute S.A., 14, chemin des Aulx, CH-1228 Plan-les-Ouates, Switzerland</mods:affiliation></affiliation></author><author><name sortKey="Gawlas, Katrin" sort="Gawlas, Katrin" uniqKey="Gawlas K" first="Katrin" last="Gawlas">Katrin Gawlas</name><affiliation><mods:affiliation>University of Nijmegen, Toernooiveld 1, NL-6525 ED Neijmegen, The Netherlands</mods:affiliation></affiliation></author><author><name sortKey="Steinmayr, Markus" sort="Steinmayr, Markus" uniqKey="Steinmayr M" first="Markus" last="Steinmayr">Markus Steinmayr</name><affiliation><mods:affiliation>Schering AG, Heinrich Heine Str. 20, D-10179 Berlin, Germany</mods:affiliation></affiliation></author><author><name sortKey="Becker Andre, Michael" sort="Becker Andre, Michael" uniqKey="Becker Andre M" first="Michael" last="Becker-André">Michael Becker-André</name><affiliation><mods:affiliation>Serono Pharmaceutical Research Institute S.A., 14, chemin des Aulx, CH-1228 Plan-les-Ouates, Switzerland</mods:affiliation></affiliation><affiliation><mods:affiliation>Corresponding author. Tel: +41-22-7069-737; Fax: +41-22-794.69.65; e-mail: michael.becker-andre@serono.com</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">Gene</title><title level="j" type="abbrev">GENE</title><idno type="ISSN">0378-1119</idno><imprint><publisher>ELSEVIER</publisher><date type="published" when="1998">1998</date><biblScope unit="volume">216</biblScope><biblScope unit="issue">2</biblScope><biblScope unit="page" from="277">277</biblScope><biblScope unit="page" to="283">283</biblScope></imprint><idno type="ISSN">0378-1119</idno></series><idno type="istex">A22D25BEBAE94025B2269BAB785D496C150DD876</idno><idno type="DOI">10.1016/S0378-1119(98)00348-5</idno><idno type="PII">S0378-1119(98)00348-5</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0378-1119</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">RORβ is a member of the nuclear hormone receptor superfamily whose ligand is unknown. Expression of RORβ is confined to the central nervous system and its pattern suggests that this orphan nuclear receptor is implicated in the processing of sensory information and in circadian timing. In rats, RORβ mRNA levels oscillate robustly in pineal gland and retina, displaying a 24h rhythm. Here we report the cloning of the cDNA of a novel isoform of RORβ from rat pineal tissue. Expression of this isoform, called RORβ2, is confined to pineal gland and retina and strongly increases at night. RORβ2 shares common DNA- and putative ligand-binding domains with the canonical RORβ (referred to as RORβ1), but is characterized by a different amino-terminal domain. This structural difference renders RORβ2 much more selectively binding to DNA than RORβ1. Moreover, in contrast to RORβ1, the novel isoform efficiently activates transcription also in non-neuronal cell lines. Thus, the two RORβ isoforms are likely to regulate different sets of genes in different physiological contexts.</div></front></TEI><istex><corpusName>elsevier</corpusName><author><json:item><name>Elisabeth André</name><affiliations><json:string>Serono Pharmaceutical Research Institute S.A., 14, chemin des Aulx, CH-1228 Plan-les-Ouates, Switzerland</json:string></affiliations></json:item><json:item><name>Katrin Gawlas</name><affiliations><json:string>University of Nijmegen, Toernooiveld 1, NL-6525 ED Neijmegen, The Netherlands</json:string></affiliations></json:item><json:item><name>Markus Steinmayr</name><affiliations><json:string>Schering AG, Heinrich Heine Str. 20, D-10179 Berlin, Germany</json:string></affiliations></json:item><json:item><name>Michael Becker-André</name><affiliations><json:string>Serono Pharmaceutical Research Institute S.A., 14, chemin des Aulx, CH-1228 Plan-les-Ouates, Switzerland</json:string><json:string>Corresponding author. Tel: +41-22-7069-737; Fax: +41-22-794.69.65; e-mail: michael.becker-andre@serono.com</json:string></affiliations></json:item></author><subject><json:item><lang><json:string>eng</json:string></lang><value>Transcriptional transactivation</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Circadian</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Zinc-finger</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>N-terminal</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>DR, Direct repeat</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>LUC, luciferase</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>PCR, polymerase chain reaction</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>RACE, rapid amplification of cDNA ends</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>ROR, retinoid-related orphan receptor</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>RORE, ROR response elements</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>RT, reverse transcription</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>tk, thymidine kinase</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>ZT, Zeitgeber time</value></json:item></subject><language><json:string>eng</json:string></language><abstract>RORβ is a member of the nuclear hormone receptor superfamily whose ligand is unknown. Expression of RORβ is confined to the central nervous system and its pattern suggests that this orphan nuclear receptor is implicated in the processing of sensory information and in circadian timing. In rats, RORβ mRNA levels oscillate robustly in pineal gland and retina, displaying a 24h rhythm. Here we report the cloning of the cDNA of a novel isoform of RORβ from rat pineal tissue. Expression of this isoform, called RORβ2, is confined to pineal gland and retina and strongly increases at night. RORβ2 shares common DNA- and putative ligand-binding domains with the canonical RORβ (referred to as RORβ1), but is characterized by a different amino-terminal domain. This structural difference renders RORβ2 much more selectively binding to DNA than RORβ1. Moreover, in contrast to RORβ1, the novel isoform efficiently activates transcription also in non-neuronal cell lines. Thus, the two RORβ isoforms are likely to regulate different sets of genes in different physiological contexts.</abstract><qualityIndicators><score>5.315</score><pdfVersion>1.2</pdfVersion><pdfPageSize>596 x 793 pts</pdfPageSize><refBibsNative>true</refBibsNative><keywordCount>13</keywordCount><abstractCharCount>1076</abstractCharCount><pdfWordCount>3311</pdfWordCount><pdfCharCount>21239</pdfCharCount><pdfPageCount>7</pdfPageCount><abstractWordCount>167</abstractWordCount></qualityIndicators><title>A novel isoform of the orphan nuclear receptor ROR β is specifically expressed in pineal gland and retina</title><pii><json:string>S0378-1119(98)00348-5</json:string></pii><genre><json:string>research-article</json:string></genre><host><volume>216</volume><pii><json:string>S0378-1119(00)X0108-4</json:string></pii><pages><last>283</last><first>277</first></pages><issn><json:string>0378-1119</json:string></issn><issue>2</issue><genre></genre><language><json:string>unknown</json:string></language><title>Gene</title><publicationDate>1998</publicationDate></host><categories><wos><json:string>BIOCHEMISTRY & MOLECULAR BIOLOGY</json:string><json:string>GENETICS & HEREDITY</json:string></wos></categories><publicationDate>1998</publicationDate><copyrightDate>1998</copyrightDate><doi><json:string>10.1016/S0378-1119(98)00348-5</json:string></doi><id>A22D25BEBAE94025B2269BAB785D496C150DD876</id><fulltext><json:item><original>true</original><mimetype>application/pdf</mimetype><extension>pdf</extension><uri>https://api.istex.fr/document/A22D25BEBAE94025B2269BAB785D496C150DD876/fulltext/pdf</uri></json:item><json:item><original>false</original><mimetype>application/zip</mimetype><extension>zip</extension><uri>https://api.istex.fr/document/A22D25BEBAE94025B2269BAB785D496C150DD876/fulltext/zip</uri></json:item><istex:fulltextTEI uri="https://api.istex.fr/document/A22D25BEBAE94025B2269BAB785D496C150DD876/fulltext/tei"><teiHeader><fileDesc><titleStmt><title level="a">A novel isoform of the orphan nuclear receptor ROR β is specifically expressed in pineal gland and retina</title></titleStmt><publicationStmt><authority>ISTEX</authority><publisher>ELSEVIER</publisher><availability><p>ELSEVIER</p></availability><date>1998</date></publicationStmt><notesStmt><note>C.M. Kane</note><note type="content">Fig. 1: Nocturnal expression of RORβ in pineal gland is upregulated both at the transcript and the protein level. (A) Northern hybridization was performed using 5μg total RNA extracted from rat pineal gland dissected during daytime (`D'; ZT6) and nighttime (`N'; ZT18), respectively. (B) Western blot experiment using rabbit antiserum raised against bacterially expressed RORβ. 15μg total protein extracted from pineal gland dissected during daytime or nighttime were loaded. The RORβ-specific signal migrating at 50kDa is indicated by an arrow.</note><note type="content">Fig. 2: RORβ2 is a novel isoform specifically expressed in pineal gland and retina. (A) Comparison of the nucleotide and amino-acid sequences of RORβ1 and RORβ2 at the level of the amino-terminal domain. The nucleotide sequence encoding the amino-terminal domain is shown in bold letters; the 5′ untranslated sequence is shown in lower case letters. For orientation, the cysteine residues of the first zinc-finger motif of the DNA-binding domain are underlined. (B) Reverse transcription PCR using total RNA extracted from various brain areas, pineal gland and retina dissected at midday (`Day'; ZT6) and midnight (`Night'; ZT18), respectively. Oligonucleotide primer pairs were used to amplify cDNA fragments encoding part of the putative ligand-binding domain (RORβ common), or cDNA fragments encoding RORβ1- or RORβ2-specific amino-terminal domains (RORβ isoform 1 and RORβ isoform 2, respectively). Amplification products were separated on agarose gels.</note><note type="content">Fig. 3: DNA binding specificity of RORβ isoforms. Electrophoretic mobility shift assay analysis of in vitro-translated RORβ1 (A) and RORβ2 (B) using 16 different double-stranded 32P-labeled oligonucleotide probes containing the nuclear receptor binding half-site AANNAGGTCA. The two varied nucleotides NN in the −1 and −2 position flanking the canonical half-site core sequence AGGTCA are indicated above each lane.</note><note type="content">Fig. 4: Transactivation of various RORE-tk-luciferase reporter genes by RORβ1 and RORβ2 in Neuro2A cells. Three different reporter plasmids were used containing upstream of the minimal thymidine kinase promoter (tk) a dimeric RORβ response element (`DR8') differing in the two nucleotide positions preceding the AGGTCA core sequence of each binding half-site (GT, TA, GC). Reporter plasmid tk.luc serves as control. Each column represents the mean value of five experiments. Standard deviations are indicated by error bars.</note><note type="content">Fig. 5: Transactivation of the optimal RORE-tk-luciferase reporter gene DR8(GT).luc by RORβ1 and RORβ2 in HeLa cells. The empty expression vector pSG5 served as a control. Each column represents the mean value of five experiments. Standard deviations are indicated by error bars.</note></notesStmt><sourceDesc><biblStruct type="inbook"><analytic><title level="a">A novel isoform of the orphan nuclear receptor ROR β is specifically expressed in pineal gland and retina</title><author><persName><forename type="first">Elisabeth</forename><surname>André</surname></persName><affiliation>Serono Pharmaceutical Research Institute S.A., 14, chemin des Aulx, CH-1228 Plan-les-Ouates, Switzerland</affiliation></author><author><persName><forename type="first">Katrin</forename><surname>Gawlas</surname></persName><affiliation>University of Nijmegen, Toernooiveld 1, NL-6525 ED Neijmegen, The Netherlands</affiliation></author><author><persName><forename type="first">Markus</forename><surname>Steinmayr</surname></persName><affiliation>Schering AG, Heinrich Heine Str. 20, D-10179 Berlin, Germany</affiliation></author><author><persName><forename type="first">Michael</forename><surname>Becker-André</surname></persName><affiliation>Serono Pharmaceutical Research Institute S.A., 14, chemin des Aulx, CH-1228 Plan-les-Ouates, Switzerland</affiliation><affiliation>Corresponding author. Tel: +41-22-7069-737; Fax: +41-22-794.69.65; e-mail: michael.becker-andre@serono.com</affiliation></author></analytic><monogr><title level="j">Gene</title><title level="j" type="abbrev">GENE</title><idno type="pISSN">0378-1119</idno><idno type="PII">S0378-1119(00)X0108-4</idno><imprint><publisher>ELSEVIER</publisher><date type="published" when="1998"></date><biblScope unit="volume">216</biblScope><biblScope unit="issue">2</biblScope><biblScope unit="page" from="277">277</biblScope><biblScope unit="page" to="283">283</biblScope></imprint></monogr><idno type="istex">A22D25BEBAE94025B2269BAB785D496C150DD876</idno><idno type="DOI">10.1016/S0378-1119(98)00348-5</idno><idno type="PII">S0378-1119(98)00348-5</idno></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>1998</date></creation><langUsage><language ident="en">en</language></langUsage><abstract xml:lang="en"><p>RORβ is a member of the nuclear hormone receptor superfamily whose ligand is unknown. Expression of RORβ is confined to the central nervous system and its pattern suggests that this orphan nuclear receptor is implicated in the processing of sensory information and in circadian timing. In rats, RORβ mRNA levels oscillate robustly in pineal gland and retina, displaying a 24h rhythm. Here we report the cloning of the cDNA of a novel isoform of RORβ from rat pineal tissue. Expression of this isoform, called RORβ2, is confined to pineal gland and retina and strongly increases at night. RORβ2 shares common DNA- and putative ligand-binding domains with the canonical RORβ (referred to as RORβ1), but is characterized by a different amino-terminal domain. This structural difference renders RORβ2 much more selectively binding to DNA than RORβ1. Moreover, in contrast to RORβ1, the novel isoform efficiently activates transcription also in non-neuronal cell lines. Thus, the two RORβ isoforms are likely to regulate different sets of genes in different physiological contexts.</p></abstract><textClass><keywords scheme="keyword"><list><head>Keywords</head><item><term>Transcriptional transactivation</term></item><item><term>Circadian</term></item><item><term>Zinc-finger</term></item><item><term>N-terminal</term></item></list></keywords></textClass><textClass><keywords scheme="keyword"><list><head>Abbreviations</head><item><term>DR, Direct repeat</term></item><item><term>LUC, luciferase</term></item><item><term>PCR, polymerase chain reaction</term></item><item><term>RACE, rapid amplification of cDNA ends</term></item><item><term>ROR, retinoid-related orphan receptor</term></item><item><term>RORE, ROR response elements</term></item><item><term>RT, reverse transcription</term></item><item><term>tk, thymidine kinase</term></item><item><term>ZT, Zeitgeber time</term></item></list></keywords></textClass></profileDesc><revisionDesc><change when="1998-06-17">Registration</change><change when="1998-06-17">Modified</change><change when="1998">Published</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><original>false</original><mimetype>text/plain</mimetype><extension>txt</extension><uri>https://api.istex.fr/document/A22D25BEBAE94025B2269BAB785D496C150DD876/fulltext/txt</uri></json:item></fulltext><metadata><istex:metadataXml wicri:clean="Elsevier, elements deleted: ce:floats; body; tail"><istex:xmlDeclaration>version="1.0" encoding="utf-8"</istex:xmlDeclaration><istex:docType PUBLIC="-//ES//DTD journal article DTD version 4.5.2//EN//XML" URI="art452.dtd" name="istex:docType"><istex:entity SYSTEM="gr1" NDATA="IMAGE" name="gr1"></istex:entity><istex:entity SYSTEM="gr2" NDATA="IMAGE" name="gr2"></istex:entity><istex:entity SYSTEM="gr3" NDATA="IMAGE" name="gr3"></istex:entity><istex:entity SYSTEM="gr4" NDATA="IMAGE" name="gr4"></istex:entity><istex:entity SYSTEM="gr5" NDATA="IMAGE" name="gr5"></istex:entity></istex:docType><istex:document><converted-article version="4.5.2" docsubtype="fla"><item-info><jid>GENE</jid><aid>11472</aid><ce:pii>S0378-1119(98)00348-5</ce:pii><ce:doi>10.1016/S0378-1119(98)00348-5</ce:doi><ce:copyright year="1998" type="full-transfer">Elsevier Science B.V.</ce:copyright></item-info><head><ce:title>A novel isoform of the orphan nuclear receptor ROR<ce:italic>β</ce:italic> is specifically expressed in pineal gland and retina</ce:title><ce:author-group><ce:author><ce:given-name>Elisabeth</ce:given-name><ce:surname>André</ce:surname><ce:cross-ref refid="AFF1">a</ce:cross-ref></ce:author><ce:author><ce:given-name>Katrin</ce:given-name><ce:surname>Gawlas</ce:surname><ce:cross-ref refid="AFF2">b</ce:cross-ref></ce:author><ce:author><ce:given-name>Markus</ce:given-name><ce:surname>Steinmayr</ce:surname><ce:cross-ref refid="AFF3">c</ce:cross-ref></ce:author><ce:author><ce:given-name>Michael</ce:given-name><ce:surname>Becker-André</ce:surname><ce:cross-ref refid="AFF1">a</ce:cross-ref><ce:cross-ref refid="CORR1">*</ce:cross-ref></ce:author><ce:affiliation id="AFF1"><ce:label>a</ce:label><ce:textfn>Serono Pharmaceutical Research Institute S.A., 14, chemin des Aulx, CH-1228 Plan-les-Ouates, Switzerland</ce:textfn></ce:affiliation><ce:affiliation id="AFF2"><ce:label>b</ce:label><ce:textfn>University of Nijmegen, Toernooiveld 1, NL-6525 ED Neijmegen, The Netherlands</ce:textfn></ce:affiliation><ce:affiliation id="AFF3"><ce:label>c</ce:label><ce:textfn>Schering AG, Heinrich Heine Str. 20, D-10179 Berlin, Germany</ce:textfn></ce:affiliation><ce:correspondence id="CORR1"><ce:label>*</ce:label><ce:text>Corresponding author. Tel: +41-22-7069-737; Fax: +41-22-794.69.65; e-mail: michael.becker-andre@serono.com</ce:text></ce:correspondence></ce:author-group><ce:date-received day="30" month="3" year="1998"></ce:date-received><ce:date-revised day="17" month="6" year="1998"></ce:date-revised><ce:date-accepted day="17" month="6" year="1998"></ce:date-accepted><ce:miscellaneous>C.M. Kane</ce:miscellaneous><ce:abstract><ce:section-title>Abstract</ce:section-title><ce:abstract-sec><ce:simple-para>ROR<ce:italic>β</ce:italic> is a member of the nuclear hormone receptor superfamily whose ligand is unknown. Expression of ROR<ce:italic>β</ce:italic> is confined to the central nervous system and its pattern suggests that this orphan nuclear receptor is implicated in the processing of sensory information and in circadian timing. In rats, ROR<ce:italic>β</ce:italic> mRNA levels oscillate robustly in pineal gland and retina, displaying a 24<ce:hsp sp="0.25"></ce:hsp>h rhythm. Here we report the cloning of the cDNA of a novel isoform of ROR<ce:italic>β</ce:italic> from rat pineal tissue. Expression of this isoform, called ROR<ce:italic>β</ce:italic>2, is confined to pineal gland and retina and strongly increases at night. ROR<ce:italic>β</ce:italic>2 shares common DNA- and putative ligand-binding domains with the canonical ROR<ce:italic>β</ce:italic> (referred to as ROR<ce:italic>β</ce:italic>1), but is characterized by a different amino-terminal domain. This structural difference renders ROR<ce:italic>β</ce:italic>2 much more selectively binding to DNA than ROR<ce:italic>β</ce:italic>1. Moreover, in contrast to ROR<ce:italic>β</ce:italic>1, the novel isoform efficiently activates transcription also in non-neuronal cell lines. Thus, the two ROR<ce:italic>β</ce:italic> isoforms are likely to regulate different sets of genes in different physiological contexts.</ce:simple-para></ce:abstract-sec></ce:abstract><ce:keywords class="keyword"><ce:section-title>Keywords</ce:section-title><ce:keyword><ce:text>Transcriptional transactivation</ce:text></ce:keyword><ce:keyword><ce:text>Circadian</ce:text></ce:keyword><ce:keyword><ce:text>Zinc-finger</ce:text></ce:keyword><ce:keyword><ce:text>N-terminal</ce:text></ce:keyword></ce:keywords><ce:keywords class="abr"><ce:section-title>Abbreviations</ce:section-title><ce:keyword><ce:text>DR, Direct repeat</ce:text></ce:keyword><ce:keyword><ce:text>LUC, luciferase</ce:text></ce:keyword><ce:keyword><ce:text>PCR, polymerase chain reaction</ce:text></ce:keyword><ce:keyword><ce:text>RACE, rapid amplification of cDNA ends</ce:text></ce:keyword><ce:keyword><ce:text>ROR, retinoid-related orphan receptor</ce:text></ce:keyword><ce:keyword><ce:text>RORE, ROR response elements</ce:text></ce:keyword><ce:keyword><ce:text>RT, reverse transcription</ce:text></ce:keyword><ce:keyword><ce:text>tk, thymidine kinase</ce:text></ce:keyword><ce:keyword><ce:text>ZT, <ce:italic>Zeitgeber</ce:italic> time</ce:text></ce:keyword></ce:keywords></head></converted-article></istex:document></istex:metadataXml><mods version="3.6"><titleInfo><title>A novel isoform of the orphan nuclear receptor ROR β is specifically expressed in pineal gland and retina</title></titleInfo><titleInfo type="alternative" contentType="CDATA"><title>A novel isoform of the orphan nuclear receptor ROR</title></titleInfo><name type="personal"><namePart type="given">Elisabeth</namePart><namePart type="family">André</namePart><affiliation>Serono Pharmaceutical Research Institute S.A., 14, chemin des Aulx, CH-1228 Plan-les-Ouates, Switzerland</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Katrin</namePart><namePart type="family">Gawlas</namePart><affiliation>University of Nijmegen, Toernooiveld 1, NL-6525 ED Neijmegen, The Netherlands</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Markus</namePart><namePart type="family">Steinmayr</namePart><affiliation>Schering AG, Heinrich Heine Str. 20, D-10179 Berlin, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Michael</namePart><namePart type="family">Becker-André</namePart><affiliation>Serono Pharmaceutical Research Institute S.A., 14, chemin des Aulx, CH-1228 Plan-les-Ouates, Switzerland</affiliation><affiliation>Corresponding author. Tel: +41-22-7069-737; Fax: +41-22-794.69.65; e-mail: michael.becker-andre@serono.com</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="research-article" displayLabel="Full-length article"></genre><originInfo><publisher>ELSEVIER</publisher><dateIssued encoding="w3cdtf">1998</dateIssued><dateValid encoding="w3cdtf">1998-06-17</dateValid><dateModified encoding="w3cdtf">1998-06-17</dateModified><copyrightDate encoding="w3cdtf">1998</copyrightDate></originInfo><language><languageTerm type="code" authority="iso639-2b">eng</languageTerm><languageTerm type="code" authority="rfc3066">en</languageTerm></language><physicalDescription><internetMediaType>text/html</internetMediaType></physicalDescription><abstract lang="en">RORβ is a member of the nuclear hormone receptor superfamily whose ligand is unknown. Expression of RORβ is confined to the central nervous system and its pattern suggests that this orphan nuclear receptor is implicated in the processing of sensory information and in circadian timing. In rats, RORβ mRNA levels oscillate robustly in pineal gland and retina, displaying a 24h rhythm. Here we report the cloning of the cDNA of a novel isoform of RORβ from rat pineal tissue. Expression of this isoform, called RORβ2, is confined to pineal gland and retina and strongly increases at night. RORβ2 shares common DNA- and putative ligand-binding domains with the canonical RORβ (referred to as RORβ1), but is characterized by a different amino-terminal domain. This structural difference renders RORβ2 much more selectively binding to DNA than RORβ1. Moreover, in contrast to RORβ1, the novel isoform efficiently activates transcription also in non-neuronal cell lines. Thus, the two RORβ isoforms are likely to regulate different sets of genes in different physiological contexts.</abstract><note>C.M. Kane</note><note type="content">Fig. 1: Nocturnal expression of RORβ in pineal gland is upregulated both at the transcript and the protein level. (A) Northern hybridization was performed using 5μg total RNA extracted from rat pineal gland dissected during daytime (`D'; ZT6) and nighttime (`N'; ZT18), respectively. (B) Western blot experiment using rabbit antiserum raised against bacterially expressed RORβ. 15μg total protein extracted from pineal gland dissected during daytime or nighttime were loaded. The RORβ-specific signal migrating at 50kDa is indicated by an arrow.</note><note type="content">Fig. 2: RORβ2 is a novel isoform specifically expressed in pineal gland and retina. (A) Comparison of the nucleotide and amino-acid sequences of RORβ1 and RORβ2 at the level of the amino-terminal domain. The nucleotide sequence encoding the amino-terminal domain is shown in bold letters; the 5′ untranslated sequence is shown in lower case letters. For orientation, the cysteine residues of the first zinc-finger motif of the DNA-binding domain are underlined. (B) Reverse transcription PCR using total RNA extracted from various brain areas, pineal gland and retina dissected at midday (`Day'; ZT6) and midnight (`Night'; ZT18), respectively. Oligonucleotide primer pairs were used to amplify cDNA fragments encoding part of the putative ligand-binding domain (RORβ common), or cDNA fragments encoding RORβ1- or RORβ2-specific amino-terminal domains (RORβ isoform 1 and RORβ isoform 2, respectively). Amplification products were separated on agarose gels.</note><note type="content">Fig. 3: DNA binding specificity of RORβ isoforms. Electrophoretic mobility shift assay analysis of in vitro-translated RORβ1 (A) and RORβ2 (B) using 16 different double-stranded 32P-labeled oligonucleotide probes containing the nuclear receptor binding half-site AANNAGGTCA. The two varied nucleotides NN in the −1 and −2 position flanking the canonical half-site core sequence AGGTCA are indicated above each lane.</note><note type="content">Fig. 4: Transactivation of various RORE-tk-luciferase reporter genes by RORβ1 and RORβ2 in Neuro2A cells. Three different reporter plasmids were used containing upstream of the minimal thymidine kinase promoter (tk) a dimeric RORβ response element (`DR8') differing in the two nucleotide positions preceding the AGGTCA core sequence of each binding half-site (GT, TA, GC). Reporter plasmid tk.luc serves as control. Each column represents the mean value of five experiments. Standard deviations are indicated by error bars.</note><note type="content">Fig. 5: Transactivation of the optimal RORE-tk-luciferase reporter gene DR8(GT).luc by RORβ1 and RORβ2 in HeLa cells. The empty expression vector pSG5 served as a control. Each column represents the mean value of five experiments. Standard deviations are indicated by error bars.</note><subject><genre>Keywords</genre><topic>Transcriptional transactivation</topic><topic>Circadian</topic><topic>Zinc-finger</topic><topic>N-terminal</topic></subject><subject><genre>Abbreviations</genre><topic>DR, Direct repeat</topic><topic>LUC, luciferase</topic><topic>PCR, polymerase chain reaction</topic><topic>RACE, rapid amplification of cDNA ends</topic><topic>ROR, retinoid-related orphan receptor</topic><topic>RORE, ROR response elements</topic><topic>RT, reverse transcription</topic><topic>tk, thymidine kinase</topic><topic>ZT, Zeitgeber time</topic></subject><relatedItem type="host"><titleInfo><title>Gene</title></titleInfo><titleInfo type="abbreviated"><title>GENE</title></titleInfo><genre type="Journal">journal</genre><originInfo><dateIssued encoding="w3cdtf">19980831</dateIssued></originInfo><identifier type="ISSN">0378-1119</identifier><identifier type="PII">S0378-1119(00)X0108-4</identifier><part><date>19980831</date><detail type="volume"><number>216</number><caption>vol.</caption></detail><detail type="issue"><number>2</number><caption>no.</caption></detail><extent unit="issue pages"><start>225</start><end>338</end></extent><extent unit="pages"><start>277</start><end>283</end></extent></part></relatedItem><identifier type="istex">A22D25BEBAE94025B2269BAB785D496C150DD876</identifier><identifier type="DOI">10.1016/S0378-1119(98)00348-5</identifier><identifier type="PII">S0378-1119(98)00348-5</identifier><accessCondition type="use and reproduction" contentType="">© 1998Elsevier Science B.V.</accessCondition><recordInfo><recordContentSource>ELSEVIER</recordContentSource><recordOrigin>Elsevier Science B.V., ©1998</recordOrigin></recordInfo></mods></metadata><enrichments><istex:catWosTEI uri="https://api.istex.fr/document/A22D25BEBAE94025B2269BAB785D496C150DD876/enrichments/catWos"><teiHeader><profileDesc><textClass><classCode scheme="WOS">BIOCHEMISTRY & MOLECULAR BIOLOGY</classCode><classCode scheme="WOS">GENETICS & HEREDITY</classCode></textClass></profileDesc></teiHeader></istex:catWosTEI></enrichments><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
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