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| Status |
Public on Dec 22, 2010 |
| Title |
Chromatin Remodeling Complex Dosage Modulates Transcription Factor Function in Heart Development |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Dominant mutations in cardiac transcription factor genes cause human inherited congenital heart defects (CHDs), but their molecular basis is not understood. Transcription factors and Brg1/Brm-associated factor (BAF) chromatin remodeling complex interactions suggest potential mechanisms, but the role of BAF complexes in cardiogenesis is not known. Here 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 relative levels of transcription factors and BAF complexes are important for heart development, which is supported by reduced occupancy of Brg1 at cardiac genes 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.
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| Overall design |
We performed transcriptional profiling of E11.5 hearts from mice heterozygous for deletions of Brg1, Tbx5, or Nkx2-5, and mice that were compound heterozygotes for Brg1 and each transcription factor gene (Tbx5 and Nkx2-5).
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| Contributor(s) |
Bruneau B, Holloway A |
| Citation(s) |
21304516 |
| Submission date |
Dec 20, 2010 |
| Last update date |
Mar 04, 2019 |
| Contact name |
Alisha Holloway |
| E-mail(s) |
alisha.holloway@gladstone.ucsf.edu
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| Organization name |
Gladstone Institutes
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| Street address |
1650 Owens Street
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| City |
San Francisco |
| State/province |
CA |
| ZIP/Postal code |
94158 |
| Country |
USA |
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| Platforms (1) |
| GPL6246 |
[MoGene-1_0-st] Affymetrix Mouse Gene 1.0 ST Array [transcript (gene) version] |
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| Samples (27)
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| Relations |
| BioProject |
PRJNA135019 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE26191_RAW.tar |
112.1 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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