Links to Exploration step
Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en"><italic>Fibroblast growth factor 10</italic>
gene regulation in the second heart field by Tbx1, Nkx2-5, and Islet1 reveals a genetic switch for down-regulation in the myocardium</title>
<author><name sortKey="Watanabe, Yusuke" sort="Watanabe, Yusuke" uniqKey="Watanabe Y" first="Yusuke" last="Watanabe">Yusuke Watanabe</name>
<affiliation><nlm:aff id="aff1">Department of Developmental Biology, Centre National de la Recherche Scientifique (CNRS) Unité de Recherche Associée 2578,<institution>Institut Pasteur</institution>
, 75015 Paris,<country>France</country>
;</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff2">Department of Developmental Neurobiology, Institute of Development, Aging and Cancer,<institution>Tohoku University</institution>
, Sendai 980-8575,<country>Japan</country>
;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Zaffran, Stephane" sort="Zaffran, Stephane" uniqKey="Zaffran S" first="Stéphane" last="Zaffran">Stéphane Zaffran</name>
<affiliation><nlm:aff id="aff3">Medical Genetics and Functional Genomics, Institut National de la Santé et de la Recherche Médicale Unité Mixte de Recherche (UMR) S910,<institution>School of Medicine of Marseille</institution>
, 13005 Marseille,<country>France</country>
;</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff4"><institution>Aix-Marseille University</institution>
, 13007 Marseille,<country>France</country>
;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Kuroiwa, Atsushi" sort="Kuroiwa, Atsushi" uniqKey="Kuroiwa A" first="Atsushi" last="Kuroiwa">Atsushi Kuroiwa</name>
<affiliation><nlm:aff id="aff5">Division of Biological Science,<institution>Graduate School of Science</institution>
, Nagoya University, Nagoya 464-8602,<country>Japan</country>
;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Higuchi, Hiroaki" sort="Higuchi, Hiroaki" uniqKey="Higuchi H" first="Hiroaki" last="Higuchi">Hiroaki Higuchi</name>
<affiliation><nlm:aff id="aff5">Division of Biological Science,<institution>Graduate School of Science</institution>
, Nagoya University, Nagoya 464-8602,<country>Japan</country>
;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Ogura, Toshihiko" sort="Ogura, Toshihiko" uniqKey="Ogura T" first="Toshihiko" last="Ogura">Toshihiko Ogura</name>
<affiliation><nlm:aff id="aff2">Department of Developmental Neurobiology, Institute of Development, Aging and Cancer,<institution>Tohoku University</institution>
, Sendai 980-8575,<country>Japan</country>
;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Harvey, Richard P" sort="Harvey, Richard P" uniqKey="Harvey R" first="Richard P." last="Harvey">Richard P. Harvey</name>
<affiliation><nlm:aff id="aff6"><institution>Victor Chang Cardiac Research Institute</institution>
, Darlinghurst 2010, NSW,<country>Australia</country>
;</nlm:aff>
</affiliation>
<affiliation><nlm:aff wicri:cut="; and" id="aff7">Faculty of Medicine, St. Vincent’s Clinical School,<institution>University of New South Wales</institution>
, Kensington 2052, NSW,<country>Australia</country>
</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Kelly, Robert G" sort="Kelly, Robert G" uniqKey="Kelly R" first="Robert G." last="Kelly">Robert G. Kelly</name>
<affiliation><nlm:aff id="aff4"><institution>Aix-Marseille University</institution>
, 13007 Marseille,<country>France</country>
;</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff8"><institution>Developmental Biology Institute of Marseille Luminy</institution>
, CNRS UMR 7288, Campus de Luminy, 13288 Marseille,<country>France</country>
</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Buckingham, Margaret" sort="Buckingham, Margaret" uniqKey="Buckingham M" first="Margaret" last="Buckingham">Margaret Buckingham</name>
<affiliation><nlm:aff id="aff1">Department of Developmental Biology, Centre National de la Recherche Scientifique (CNRS) Unité de Recherche Associée 2578,<institution>Institut Pasteur</institution>
, 75015 Paris,<country>France</country>
;</nlm:aff>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PMC</idno>
<idno type="pmid">23093675</idno>
<idno type="pmc">3494960</idno>
<idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3494960</idno>
<idno type="RBID">PMC:3494960</idno>
<idno type="doi">10.1073/pnas.1215360109</idno>
<date when="2012">2012</date>
<idno type="wicri:Area/Pmc/Corpus">001B74</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">001B74</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main"><italic>Fibroblast growth factor 10</italic>
gene regulation in the second heart field by Tbx1, Nkx2-5, and Islet1 reveals a genetic switch for down-regulation in the myocardium</title>
<author><name sortKey="Watanabe, Yusuke" sort="Watanabe, Yusuke" uniqKey="Watanabe Y" first="Yusuke" last="Watanabe">Yusuke Watanabe</name>
<affiliation><nlm:aff id="aff1">Department of Developmental Biology, Centre National de la Recherche Scientifique (CNRS) Unité de Recherche Associée 2578,<institution>Institut Pasteur</institution>
, 75015 Paris,<country>France</country>
;</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff2">Department of Developmental Neurobiology, Institute of Development, Aging and Cancer,<institution>Tohoku University</institution>
, Sendai 980-8575,<country>Japan</country>
;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Zaffran, Stephane" sort="Zaffran, Stephane" uniqKey="Zaffran S" first="Stéphane" last="Zaffran">Stéphane Zaffran</name>
<affiliation><nlm:aff id="aff3">Medical Genetics and Functional Genomics, Institut National de la Santé et de la Recherche Médicale Unité Mixte de Recherche (UMR) S910,<institution>School of Medicine of Marseille</institution>
, 13005 Marseille,<country>France</country>
;</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff4"><institution>Aix-Marseille University</institution>
, 13007 Marseille,<country>France</country>
;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Kuroiwa, Atsushi" sort="Kuroiwa, Atsushi" uniqKey="Kuroiwa A" first="Atsushi" last="Kuroiwa">Atsushi Kuroiwa</name>
<affiliation><nlm:aff id="aff5">Division of Biological Science,<institution>Graduate School of Science</institution>
, Nagoya University, Nagoya 464-8602,<country>Japan</country>
;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Higuchi, Hiroaki" sort="Higuchi, Hiroaki" uniqKey="Higuchi H" first="Hiroaki" last="Higuchi">Hiroaki Higuchi</name>
<affiliation><nlm:aff id="aff5">Division of Biological Science,<institution>Graduate School of Science</institution>
, Nagoya University, Nagoya 464-8602,<country>Japan</country>
;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Ogura, Toshihiko" sort="Ogura, Toshihiko" uniqKey="Ogura T" first="Toshihiko" last="Ogura">Toshihiko Ogura</name>
<affiliation><nlm:aff id="aff2">Department of Developmental Neurobiology, Institute of Development, Aging and Cancer,<institution>Tohoku University</institution>
, Sendai 980-8575,<country>Japan</country>
;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Harvey, Richard P" sort="Harvey, Richard P" uniqKey="Harvey R" first="Richard P." last="Harvey">Richard P. Harvey</name>
<affiliation><nlm:aff id="aff6"><institution>Victor Chang Cardiac Research Institute</institution>
, Darlinghurst 2010, NSW,<country>Australia</country>
;</nlm:aff>
</affiliation>
<affiliation><nlm:aff wicri:cut="; and" id="aff7">Faculty of Medicine, St. Vincent’s Clinical School,<institution>University of New South Wales</institution>
, Kensington 2052, NSW,<country>Australia</country>
</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Kelly, Robert G" sort="Kelly, Robert G" uniqKey="Kelly R" first="Robert G." last="Kelly">Robert G. Kelly</name>
<affiliation><nlm:aff id="aff4"><institution>Aix-Marseille University</institution>
, 13007 Marseille,<country>France</country>
;</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff8"><institution>Developmental Biology Institute of Marseille Luminy</institution>
, CNRS UMR 7288, Campus de Luminy, 13288 Marseille,<country>France</country>
</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Buckingham, Margaret" sort="Buckingham, Margaret" uniqKey="Buckingham M" first="Margaret" last="Buckingham">Margaret Buckingham</name>
<affiliation><nlm:aff id="aff1">Department of Developmental Biology, Centre National de la Recherche Scientifique (CNRS) Unité de Recherche Associée 2578,<institution>Institut Pasteur</institution>
, 75015 Paris,<country>France</country>
;</nlm:aff>
</affiliation>
</author>
</analytic>
<series><title level="j">Proceedings of the National Academy of Sciences of the United States of America</title>
<idno type="ISSN">0027-8424</idno>
<idno type="eISSN">1091-6490</idno>
<imprint><date when="2012">2012</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass></textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><p>During cardiogenesis, <italic>Fibroblast Growth Factor</italic>
(<italic>Fgf10</italic>
) is expressed in the anterior second heart field. Together with Fibroblast growth factor 8 (Fgf8), Fgf10 promotes the proliferation of these cardiac progenitor cells that form the arterial pole of the heart. We have identified a 1.7-kb region in the first intron of <italic>Fgf10</italic>
that is necessary and sufficient to direct transgene expression in this cardiac context. The 1.7-kb sequence is directly controlled by T-box transcription factor 1 (Tbx1) in anterior second heart field cells that contribute to the outflow tract. It also responds to both NK2 transcription factor related, locus 5 (Nkx2-5) and ISL1 transcription factor, LIM/homeodomain (Islet1), acting through overlapping sites. Mutation of these sites reduces transgene expression in the anterior second heart field where the <italic>Fgf10</italic>
regulatory element is activated by Islet1 via direct binding in vivo. Analysis of the response to <italic>Nkx2-5</italic>
loss- and <italic>Isl1</italic>
gain-of-function genetic backgrounds indicates that the observed up-regulation of its activity in <italic>Nkx2-5</italic>
mutant hearts, reflecting that of <italic>Fgf10</italic>
, is due to the absence of Nkx2-5 repression and to up-regulation of <italic>Isl1</italic>
, normally repressed in the myocardium by Nkx2-5. ChIP experiments show strong binding of Nkx2-5 in differentiated myocardium. Molecular and genetic analysis of the <italic>Fgf10</italic>
cardiac element therefore reveals how key cardiac transcription factors orchestrate gene expression in the anterior second heart field and how genes, such as <italic>Fgf10</italic>
, normally expressed in the progenitor cell population, are repressed when these cells enter the heart and differentiate into myocardium. Our findings provide a paradigm for transcriptional mechanisms that underlie the changes in regulatory networks during the transition from progenitor state to that of the differentiated tissue.</p>
</div>
</front>
</TEI>
<pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Proc Natl Acad Sci U S A</journal-id>
<journal-id journal-id-type="iso-abbrev">Proc. Natl. Acad. Sci. U.S.A</journal-id>
<journal-id journal-id-type="hwp">pnas</journal-id>
<journal-id journal-id-type="pmc">pnas</journal-id>
<journal-id journal-id-type="publisher-id">PNAS</journal-id>
<journal-title-group><journal-title>Proceedings of the National Academy of Sciences of the United States of America</journal-title>
</journal-title-group>
<issn pub-type="ppub">0027-8424</issn>
<issn pub-type="epub">1091-6490</issn>
<publisher><publisher-name>National Academy of Sciences</publisher-name>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">23093675</article-id>
<article-id pub-id-type="pmc">3494960</article-id>
<article-id pub-id-type="publisher-id">201215360</article-id>
<article-id pub-id-type="doi">10.1073/pnas.1215360109</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Biological Sciences</subject>
<subj-group><subject>Developmental Biology</subject>
</subj-group>
</subj-group>
<series-title>Inaugural Article</series-title>
</article-categories>
<title-group><article-title><italic>Fibroblast growth factor 10</italic>
gene regulation in the second heart field by Tbx1, Nkx2-5, and Islet1 reveals a genetic switch for down-regulation in the myocardium</article-title>
<alt-title alt-title-type="short"><italic>Fgf10</italic>
gene regulation during cardiogenesis</alt-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Watanabe</surname>
<given-names>Yusuke</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>a</sup>
</xref>
<xref ref-type="aff" rid="aff2"><sup>b</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Zaffran</surname>
<given-names>Stéphane</given-names>
</name>
<xref ref-type="aff" rid="aff3"><sup>c</sup>
</xref>
<xref ref-type="aff" rid="aff4"><sup>d</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Kuroiwa</surname>
<given-names>Atsushi</given-names>
</name>
<xref ref-type="aff" rid="aff5"><sup>e</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Higuchi</surname>
<given-names>Hiroaki</given-names>
</name>
<xref ref-type="aff" rid="aff5"><sup>e</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Ogura</surname>
<given-names>Toshihiko</given-names>
</name>
<xref ref-type="aff" rid="aff2"><sup>b</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Harvey</surname>
<given-names>Richard P.</given-names>
</name>
<xref ref-type="aff" rid="aff6"><sup>f</sup>
</xref>
<xref ref-type="aff" rid="aff7"><sup>g</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Kelly</surname>
<given-names>Robert G.</given-names>
</name>
<xref ref-type="aff" rid="aff4"><sup>d</sup>
</xref>
<xref ref-type="aff" rid="aff8"><sup>h</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Buckingham</surname>
<given-names>Margaret</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>a</sup>
</xref>
<xref ref-type="corresp" rid="cor1"><sup>1</sup>
</xref>
</contrib>
<aff id="aff1"><sup>a</sup>
Department of Developmental Biology, Centre National de la Recherche Scientifique (CNRS) Unité de Recherche Associée 2578,<institution>Institut Pasteur</institution>
, 75015 Paris,<country>France</country>
;</aff>
<aff id="aff2"><sup>b</sup>
Department of Developmental Neurobiology, Institute of Development, Aging and Cancer,<institution>Tohoku University</institution>
, Sendai 980-8575,<country>Japan</country>
;</aff>
<aff id="aff3"><sup>c</sup>
Medical Genetics and Functional Genomics, Institut National de la Santé et de la Recherche Médicale Unité Mixte de Recherche (UMR) S910,<institution>School of Medicine of Marseille</institution>
, 13005 Marseille,<country>France</country>
;</aff>
<aff id="aff4"><sup>d</sup>
<institution>Aix-Marseille University</institution>
, 13007 Marseille,<country>France</country>
;</aff>
<aff id="aff5"><sup>e</sup>
Division of Biological Science,<institution>Graduate School of Science</institution>
, Nagoya University, Nagoya 464-8602,<country>Japan</country>
;</aff>
<aff id="aff6"><sup>f</sup>
<institution>Victor Chang Cardiac Research Institute</institution>
, Darlinghurst 2010, NSW,<country>Australia</country>
;</aff>
<aff id="aff7"><sup>g</sup>
Faculty of Medicine, St. Vincent’s Clinical School,<institution>University of New South Wales</institution>
, Kensington 2052, NSW,<country>Australia</country>
; and</aff>
<aff id="aff8"><sup>h</sup>
<institution>Developmental Biology Institute of Marseille Luminy</institution>
, CNRS UMR 7288, Campus de Luminy, 13288 Marseille,<country>France</country>
</aff>
</contrib-group>
<author-notes><corresp id="cor1"><sup>1</sup>
To whom correspondence should be addressed. E-mail: <email>margaret.buckingham@pasteur.fr</email>
.</corresp>
<fn fn-type="edited-by"><p>This contribution is part of the special series of Inaugural Articles by members of the National Academy of Sciences elected in 2011.</p>
</fn>
<fn fn-type="edited-by"><p>Contributed by Margaret Buckingham, September 20, 2012 (sent for review June 13, 2012)</p>
</fn>
<fn fn-type="con"><p>Author contributions: Y.W. and M.B. designed research; Y.W., S.Z., and R.G.K. performed research; A.K., H.H., R.P.H., and R.G.K. contributed new reagents/analytic tools; Y.W., S.Z., T.O., R.P.H., R.G.K., and M.B. analyzed data; and.Y.W. and M.B. wrote the paper.</p>
</fn>
</author-notes>
<pub-date pub-type="ppub"><day>6</day>
<month>11</month>
<year>2012</year>
</pub-date>
<pub-date pub-type="epub"><day>04</day>
<month>10</month>
<year>2012</year>
</pub-date>
<volume>109</volume>
<issue>45</issue>
<fpage>18273</fpage>
<lpage>18280</lpage>
<self-uri xlink:title="pdf" xlink:type="simple" xlink:href="pnas.201215360.pdf"></self-uri>
<abstract><p>During cardiogenesis, <italic>Fibroblast Growth Factor</italic>
(<italic>Fgf10</italic>
) is expressed in the anterior second heart field. Together with Fibroblast growth factor 8 (Fgf8), Fgf10 promotes the proliferation of these cardiac progenitor cells that form the arterial pole of the heart. We have identified a 1.7-kb region in the first intron of <italic>Fgf10</italic>
that is necessary and sufficient to direct transgene expression in this cardiac context. The 1.7-kb sequence is directly controlled by T-box transcription factor 1 (Tbx1) in anterior second heart field cells that contribute to the outflow tract. It also responds to both NK2 transcription factor related, locus 5 (Nkx2-5) and ISL1 transcription factor, LIM/homeodomain (Islet1), acting through overlapping sites. Mutation of these sites reduces transgene expression in the anterior second heart field where the <italic>Fgf10</italic>
regulatory element is activated by Islet1 via direct binding in vivo. Analysis of the response to <italic>Nkx2-5</italic>
loss- and <italic>Isl1</italic>
gain-of-function genetic backgrounds indicates that the observed up-regulation of its activity in <italic>Nkx2-5</italic>
mutant hearts, reflecting that of <italic>Fgf10</italic>
, is due to the absence of Nkx2-5 repression and to up-regulation of <italic>Isl1</italic>
, normally repressed in the myocardium by Nkx2-5. ChIP experiments show strong binding of Nkx2-5 in differentiated myocardium. Molecular and genetic analysis of the <italic>Fgf10</italic>
cardiac element therefore reveals how key cardiac transcription factors orchestrate gene expression in the anterior second heart field and how genes, such as <italic>Fgf10</italic>
, normally expressed in the progenitor cell population, are repressed when these cells enter the heart and differentiate into myocardium. Our findings provide a paradigm for transcriptional mechanisms that underlie the changes in regulatory networks during the transition from progenitor state to that of the differentiated tissue.</p>
</abstract>
<kwd-group><kwd>mouse embryo</kwd>
<kwd>transcriptional regulation</kwd>
</kwd-group>
</article-meta>
</front>
</pmc>
</record>
Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Asie/explor/AustralieFrV1/Data/Pmc/Corpus
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 001B74 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Pmc/Corpus/biblio.hfd -nk 001B74 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien |wiki= Wicri/Asie |area= AustralieFrV1 |flux= Pmc |étape= Corpus |type= RBID |clé= |texte= }}
![]() | This area was generated with Dilib version V0.6.33. | ![]() |