Searching across hundreds of databases

Our searching services are busy right now. Your search will reload in five seconds.

Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

Chromatin remodelling complex dosage modulates transcription factor function in heart development.

Nature communications | Feb 8, 2011

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.

Pubmed ID: 21304516 RIS Download

Mesh terms: Adaptor Proteins, Signal Transducing | Animals | Chromatin Immunoprecipitation | DNA Helicases | DNA Primers | Echocardiography | Electrocardiography | Gene Dosage | Haploinsufficiency | Heart | Heart Defects, Congenital | Homeobox Protein Nkx-2.5 | Homeodomain Proteins | Mice | Microarray Analysis | Morphogenesis | Multiprotein Complexes | NIH 3T3 Cells | Nuclear Proteins | T-Box Domain Proteins | Transcription Factors | Zebrafish | Zebrafish Proteins

Research resources used in this publication

None found

Research tools detected in this publication

Data used in this publication

None found

Associated grants

  • Agency: NHLBI NIH HHS, Id: R01 HL085860
  • Agency: NHLBI NIH HHS, Id: R01 HL085860-05
  • Agency: Canadian Institutes of Health Research, Id: 86663
  • Agency: NHLBI NIH HHS, Id: R01 HL054737
  • Agency: NHLBI NIH HHS, Id: R01 HL54737
  • Agency: NCRR NIH HHS, Id: C06 RR018928

ZFIN (Data, Gene Expression)

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.

This is a list of tools and resources that we have found mentioned in this publication.

Amira 3D analysis

A multifaceted 3D software used for visualizing, manipulating, and understanding data from tomography, microscopy, MRI and other imaging processes. Its features include: flexible import and export options; processes such as 3D image filtering and DTI based fiber tracking; visualization options, such as multichannel rendering and volume and surface rendering; and authoring tools for virtual reality navigation, video generation, and more.


View all literature mentions