Chromatin remodelling complex dosage modulates transcription factor function in heart development

Jun K. Takeuchi, Xin Lou, Jeffrey M. Alexander, Hiroe Sugizaki, Paul Delgado-Olguín, Alisha K. Holloway, Alessandro D. Mori, John N. Wylie, Chantilly Munson, Yonghong Zhu, Yu-Qing Zhou, Ru-Fang Yeh, R. Mark Henkelman, Richard P. Harvey, Daniel Metzger, Pierre Chambon, Didier Y. R. Stainier, Katherine S. Pollard, Ian C. Scott and Benoit G. Bruneau ()
Additional contact information
Jun K. Takeuchi: Gladstone Institute of Cardiovascular Disease
Xin Lou: Program in Developmental and Stem Cell Biology, The Hospital for Sick Children
Jeffrey M. Alexander: Gladstone Institute of Cardiovascular Disease
Hiroe Sugizaki: Cardiovascular Regeneration, Institute of Molecular and Cellular Biosciences, and Biological Sciences, Graduate School of Sciences, The University of Tokyo Bunkyo-ku, Tokyo 113-0032, JST PRESTO, Japan.
Paul Delgado-Olguín: Gladstone Institute of Cardiovascular Disease
Alisha K. Holloway: Gladstone Institute of Cardiovascular Disease
Alessandro D. Mori: Gladstone Institute of Cardiovascular Disease
John N. Wylie: Gladstone Institute of Cardiovascular Disease
Chantilly Munson: Cardiovascular Research Institute, University of California
Yonghong Zhu: Program in Developmental and Stem Cell Biology, The Hospital for Sick Children
Yu-Qing Zhou: The Mouse Imaging Centre, The Hospital for Sick Children
Ru-Fang Yeh: University of California
R. Mark Henkelman: The Mouse Imaging Centre, The Hospital for Sick Children
Richard P. Harvey: Victor Chang Cardiac Research Institute
Daniel Metzger: Institut de Génétique et de Biologie Moléculaire et Cellulaire, Université de Strasbourg
Pierre Chambon: Institut de Génétique et de Biologie Moléculaire et Cellulaire, Université de Strasbourg
Didier Y. R. Stainier: Programs in Biomedical Sciences and Developmental and Stem Cell Biology, University of California
Katherine S. Pollard: Gladstone Institute of Cardiovascular Disease
Ian C. Scott: Program in Developmental and Stem Cell Biology, The Hospital for Sick Children
Benoit G. Bruneau: Gladstone Institute of Cardiovascular Disease

Nature Communications, 2011, vol. 2, issue 1, 1-11

Abstract: 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 Brg1 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 Tbx5 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.

Date: 2011
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/ncomms1187 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:2:y:2011:i:1:d:10.1038_ncomms1187

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms1187

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().