Chromatin remodelling complex dosage modulates transcription factor function in heart development
Identifieur interne : 006209 ( Main/Exploration ); précédent : 006208; suivant : 006210Chromatin remodelling complex dosage modulates transcription factor function in heart development
Auteurs : Jun K. Takeuchi [États-Unis, Japon] ; Xin Lou [Canada] ; Jeffrey M. Alexander [États-Unis] ; Hiroe Sugizaki [Japon] ; Paul Delgado-Olguín [États-Unis] ; Alisha K. Holloway [États-Unis] ; Alessandro D. Mori [États-Unis] ; John N. Wylie [États-Unis] ; Chantilly Munson [États-Unis] ; Yonghong Zhu [Canada] ; Yu-Qing Zhou [Canada] ; Ru-Fang Yeh [États-Unis] ; R. Mark Henkelman [Canada] ; Richard P. Harvey [Australie] ; Daniel Metzger [France] ; Pierre Chambon [France] ; Didier Y. R. Stainier [États-Unis] ; Katherine S. Pollard [États-Unis] ; Ian C. Scott [Canada] ; Benoit G. Bruneau [États-Unis]Source :
- Nature Communications [ 2041-1723 ] ; 2011.
Abstract
Dominant mutations in cardiac transcription factor genes cause human inherited congenital heart defects (CHDs); however, their molecular basis is not understood. Interactions between transcription factors and the Brg1/Brm-associated factor (BAF) chromatin remodelling complex suggest potential mechanisms; however, the role of BAF complexes in cardiogenesis is not known. In this study, we show that dosage of Brg1 is critical for mouse and zebrafish cardiogenesis. Disrupting the balance between Brg1 and disease-causing cardiac transcription factors, including Tbx5, Tbx20 and Nkx2–5, causes severe cardiac anomalies, revealing an essential allelic balance between
Url:
DOI: 10.1038/ncomms1187
PubMed: 21304516
PubMed Central: 3096875
Affiliations:
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<affiliation><nlm:aff id="a15">These authors contributed equally to this work.</nlm:aff>
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<affiliation><nlm:aff id="a15">These authors contributed equally to this work.</nlm:aff>
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<author><name sortKey="Zhu, Yonghong" sort="Zhu, Yonghong" uniqKey="Zhu Y" first="Yonghong" last="Zhu">Yonghong Zhu</name>
<affiliation wicri:level="1"><nlm:aff id="a3"><institution>Program in Developmental and Stem Cell Biology, The Hospital for Sick Children</institution>
, Toronto, Ontario M5G 1X8,<country>Canada</country>
.</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Zhou, Yu Qing" sort="Zhou, Yu Qing" uniqKey="Zhou Y" first="Yu-Qing" last="Zhou">Yu-Qing Zhou</name>
<affiliation wicri:level="1"><nlm:aff id="a7"><institution>The Mouse Imaging Centre, The Hospital for Sick Children</institution>
, Toronto, Ontario M5G 1X8,<country>Canada</country>
.</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Yeh, Ru Fang" sort="Yeh, Ru Fang" uniqKey="Yeh R" first="Ru-Fang" last="Yeh">Ru-Fang Yeh</name>
<affiliation wicri:level="1"><nlm:aff id="a8"><institution>Department of Epidemiology and Biostatistics, University of California</institution>
, San Francisco, California 94107,<country>USA</country>
.</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Henkelman, R Mark" sort="Henkelman, R Mark" uniqKey="Henkelman R" first="R. Mark" last="Henkelman">R. Mark Henkelman</name>
<affiliation wicri:level="1"><nlm:aff id="a7"><institution>The Mouse Imaging Centre, The Hospital for Sick Children</institution>
, Toronto, Ontario M5G 1X8,<country>Canada</country>
.</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="a9"><institution>Department of Medical Biophysics, University of Toronto</institution>
, Toronto, Ontario M5S 1A8,<country>Canada</country>
.</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</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 wicri:level="1"><nlm:aff id="a10"><institution>Victor Chang Cardiac Research Institute</institution>
, Darlinghurst, Sydney 2010,<country>Australia</country>
.</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="a11"><institution>Faculty of Medicine, University of New South Wales</institution>
, Kensington 2052,<country>Australia</country>
.</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Metzger, Daniel" sort="Metzger, Daniel" uniqKey="Metzger D" first="Daniel" last="Metzger">Daniel Metzger</name>
<affiliation wicri:level="1"><nlm:aff id="a12"><institution>Institut de Génétique et de Biologie Moléculaire et Cellulaire, Université de Strasbourg</institution>
, 1 rue Laurent Fries, Illkirch 67404,<country>France</country>
.</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Chambon, Pierre" sort="Chambon, Pierre" uniqKey="Chambon P" first="Pierre" last="Chambon">Pierre Chambon</name>
<affiliation wicri:level="1"><nlm:aff id="a12"><institution>Institut de Génétique et de Biologie Moléculaire et Cellulaire, Université de Strasbourg</institution>
, 1 rue Laurent Fries, Illkirch 67404,<country>France</country>
.</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Stainier, Didier Y R" sort="Stainier, Didier Y R" uniqKey="Stainier D" first="Didier Y. R." last="Stainier">Didier Y. R. Stainier</name>
<affiliation wicri:level="1"><nlm:aff id="a4"><institution>Programs in Biomedical Sciences and Developmental and Stem Cell Biology, University of California</institution>
, San Francisco, California 94143,<country>USA</country>
.</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="a5"><institution>Cardiovascular Research Institute, University of California</institution>
, San Francisco, California 94158,<country>USA</country>
.</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="a6"><institution>Department of Biochemistry and Biophysics, University of California</institution>
, San Francisco, California 94158,<country>USA</country>
.</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Pollard, Katherine S" sort="Pollard, Katherine S" uniqKey="Pollard K" first="Katherine S." last="Pollard">Katherine S. Pollard</name>
<affiliation wicri:level="1"><nlm:aff id="a1"><institution>Gladstone Institute of Cardiovascular Disease</institution>
, San Francisco, California 94158,<country>USA</country>
.</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="a8"><institution>Department of Epidemiology and Biostatistics, University of California</institution>
, San Francisco, California 94107,<country>USA</country>
.</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Scott, Ian C" sort="Scott, Ian C" uniqKey="Scott I" first="Ian C." last="Scott">Ian C. Scott</name>
<affiliation wicri:level="1"><nlm:aff id="a3"><institution>Program in Developmental and Stem Cell Biology, The Hospital for Sick Children</institution>
, Toronto, Ontario M5G 1X8,<country>Canada</country>
.</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="a13"><institution>Department of Molecular Genetics, University of Toronto</institution>
, Toronto, Ontario M5S 1A8,<country>Canada</country>
.</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Bruneau, Benoit G" sort="Bruneau, Benoit G" uniqKey="Bruneau B" first="Benoit G." last="Bruneau">Benoit G. Bruneau</name>
<affiliation wicri:level="1"><nlm:aff id="a1"><institution>Gladstone Institute of Cardiovascular Disease</institution>
, San Francisco, California 94158,<country>USA</country>
.</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="a4"><institution>Programs in Biomedical Sciences and Developmental and Stem Cell Biology, University of California</institution>
, San Francisco, California 94143,<country>USA</country>
.</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="a5"><institution>Cardiovascular Research Institute, University of California</institution>
, San Francisco, California 94158,<country>USA</country>
.</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="a14"><institution>Department of Pediatrics, University of California</institution>
, San Francisco, California 94143,<country>USA</country>
.</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
</analytic>
<series><title level="j">Nature Communications</title>
<idno type="eISSN">2041-1723</idno>
<imprint><date when="2011">2011</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass></textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><p>Dominant mutations in cardiac transcription factor genes cause human inherited congenital heart defects (CHDs); however, their molecular basis is not understood. Interactions between transcription factors and the Brg1/Brm-associated factor (BAF) chromatin remodelling complex suggest potential mechanisms; however, the role of BAF complexes in cardiogenesis is not known. In this study, we show that dosage of Brg1 is critical for mouse and zebrafish cardiogenesis. Disrupting the balance between Brg1 and disease-causing cardiac transcription factors, including Tbx5, Tbx20 and Nkx2–5, causes severe cardiac anomalies, revealing an essential allelic balance between <italic>Brg1</italic>
and these cardiac transcription factor genes. This suggests that the relative levels of transcription factors and BAF complexes are important for heart development, which is supported by reduced occupancy of Brg1 at cardiac gene promoters in <italic>Tbx5</italic>
haploinsufficient hearts. Our results reveal complex dosage-sensitive interdependence between transcription factors and BAF complexes, providing a potential mechanism underlying transcription factor haploinsufficiency, with implications for multigenic inheritance of CHDs.</p>
</div>
</front>
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</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Benjamini, Y" uniqKey="Benjamini Y">Y. Benjamini</name>
</author>
<author><name sortKey="Hochberg, Y" uniqKey="Hochberg Y">Y. Hochberg</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Pollard, K S" uniqKey="Pollard K">K. S. Pollard</name>
</author>
<author><name sortKey="M J, Van Der Laan" uniqKey="M J V">van der Laan. M. J.</name>
</author>
</analytic>
</biblStruct>
</listBibl>
</div1>
</back>
</TEI>
<affiliations><list><country><li>Australie</li>
<li>Canada</li>
<li>France</li>
<li>Japon</li>
<li>États-Unis</li>
</country>
</list>
<tree><country name="États-Unis"><noRegion><name sortKey="Takeuchi, Jun K" sort="Takeuchi, Jun K" uniqKey="Takeuchi J" first="Jun K." last="Takeuchi">Jun K. Takeuchi</name>
</noRegion>
<name sortKey="Alexander, Jeffrey M" sort="Alexander, Jeffrey M" uniqKey="Alexander J" first="Jeffrey M." last="Alexander">Jeffrey M. Alexander</name>
<name sortKey="Alexander, Jeffrey M" sort="Alexander, Jeffrey M" uniqKey="Alexander J" first="Jeffrey M." last="Alexander">Jeffrey M. Alexander</name>
<name sortKey="Bruneau, Benoit G" sort="Bruneau, Benoit G" uniqKey="Bruneau B" first="Benoit G." last="Bruneau">Benoit G. Bruneau</name>
<name sortKey="Bruneau, Benoit G" sort="Bruneau, Benoit G" uniqKey="Bruneau B" first="Benoit G." last="Bruneau">Benoit G. Bruneau</name>
<name sortKey="Bruneau, Benoit G" sort="Bruneau, Benoit G" uniqKey="Bruneau B" first="Benoit G." last="Bruneau">Benoit G. Bruneau</name>
<name sortKey="Bruneau, Benoit G" sort="Bruneau, Benoit G" uniqKey="Bruneau B" first="Benoit G." last="Bruneau">Benoit G. Bruneau</name>
<name sortKey="Delgado Olguin, Paul" sort="Delgado Olguin, Paul" uniqKey="Delgado Olguin P" first="Paul" last="Delgado-Olguín">Paul Delgado-Olguín</name>
<name sortKey="Holloway, Alisha K" sort="Holloway, Alisha K" uniqKey="Holloway A" first="Alisha K." last="Holloway">Alisha K. Holloway</name>
<name sortKey="Mori, Alessandro D" sort="Mori, Alessandro D" uniqKey="Mori A" first="Alessandro D." last="Mori">Alessandro D. Mori</name>
<name sortKey="Munson, Chantilly" sort="Munson, Chantilly" uniqKey="Munson C" first="Chantilly" last="Munson">Chantilly Munson</name>
<name sortKey="Munson, Chantilly" sort="Munson, Chantilly" uniqKey="Munson C" first="Chantilly" last="Munson">Chantilly Munson</name>
<name sortKey="Pollard, Katherine S" sort="Pollard, Katherine S" uniqKey="Pollard K" first="Katherine S." last="Pollard">Katherine S. Pollard</name>
<name sortKey="Pollard, Katherine S" sort="Pollard, Katherine S" uniqKey="Pollard K" first="Katherine S." last="Pollard">Katherine S. Pollard</name>
<name sortKey="Stainier, Didier Y R" sort="Stainier, Didier Y R" uniqKey="Stainier D" first="Didier Y. R." last="Stainier">Didier Y. R. Stainier</name>
<name sortKey="Stainier, Didier Y R" sort="Stainier, Didier Y R" uniqKey="Stainier D" first="Didier Y. R." last="Stainier">Didier Y. R. Stainier</name>
<name sortKey="Stainier, Didier Y R" sort="Stainier, Didier Y R" uniqKey="Stainier D" first="Didier Y. R." last="Stainier">Didier Y. R. Stainier</name>
<name sortKey="Wylie, John N" sort="Wylie, John N" uniqKey="Wylie J" first="John N." last="Wylie">John N. Wylie</name>
<name sortKey="Yeh, Ru Fang" sort="Yeh, Ru Fang" uniqKey="Yeh R" first="Ru-Fang" last="Yeh">Ru-Fang Yeh</name>
</country>
<country name="Japon"><noRegion><name sortKey="Takeuchi, Jun K" sort="Takeuchi, Jun K" uniqKey="Takeuchi J" first="Jun K." last="Takeuchi">Jun K. Takeuchi</name>
</noRegion>
<name sortKey="Sugizaki, Hiroe" sort="Sugizaki, Hiroe" uniqKey="Sugizaki H" first="Hiroe" last="Sugizaki">Hiroe Sugizaki</name>
</country>
<country name="Canada"><noRegion><name sortKey="Lou, Xin" sort="Lou, Xin" uniqKey="Lou X" first="Xin" last="Lou">Xin Lou</name>
</noRegion>
<name sortKey="Henkelman, R Mark" sort="Henkelman, R Mark" uniqKey="Henkelman R" first="R. Mark" last="Henkelman">R. Mark Henkelman</name>
<name sortKey="Henkelman, R Mark" sort="Henkelman, R Mark" uniqKey="Henkelman R" first="R. Mark" last="Henkelman">R. Mark Henkelman</name>
<name sortKey="Scott, Ian C" sort="Scott, Ian C" uniqKey="Scott I" first="Ian C." last="Scott">Ian C. Scott</name>
<name sortKey="Scott, Ian C" sort="Scott, Ian C" uniqKey="Scott I" first="Ian C." last="Scott">Ian C. Scott</name>
<name sortKey="Zhou, Yu Qing" sort="Zhou, Yu Qing" uniqKey="Zhou Y" first="Yu-Qing" last="Zhou">Yu-Qing Zhou</name>
<name sortKey="Zhu, Yonghong" sort="Zhu, Yonghong" uniqKey="Zhu Y" first="Yonghong" last="Zhu">Yonghong Zhu</name>
</country>
<country name="Australie"><noRegion><name sortKey="Harvey, Richard P" sort="Harvey, Richard P" uniqKey="Harvey R" first="Richard P." last="Harvey">Richard P. Harvey</name>
</noRegion>
<name sortKey="Harvey, Richard P" sort="Harvey, Richard P" uniqKey="Harvey R" first="Richard P." last="Harvey">Richard P. Harvey</name>
</country>
<country name="France"><noRegion><name sortKey="Metzger, Daniel" sort="Metzger, Daniel" uniqKey="Metzger D" first="Daniel" last="Metzger">Daniel Metzger</name>
</noRegion>
<name sortKey="Chambon, Pierre" sort="Chambon, Pierre" uniqKey="Chambon P" first="Pierre" last="Chambon">Pierre Chambon</name>
</country>
</tree>
</affiliations>
</record>
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