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Dose-dependent sensitivity of human 3D chromatin to a heart disease-linked transcription factor [RNA-Seq 2]

GSE307021 Homo sapiens Expression profiling by high throughput sequencing 6 samples Submitted 2026/07/08 Platform GPL34281
Summary
Dosage-sensitive transcription factors (TFs) underlie altered gene regulation in human developmental disorders, and cell type-specific gene regulation is linked to the reorganization of three-dimensional (3D) chromatin during cellular differentiation. Here, we show dose-dependent regulation of chromatin organization by the congenital heart disease (CHD)-linked, lineage-restricted TF TBX5 in human cardiomyocyte differentiation. Genome organization, including compartments, topologically associated domains, and chromatin loops, are sensitive to reduced TBX5 dosage in a human model of CHD, with variations in response across individual cells. Cohesin binding was dose-dependently reduced at TBX5-bound enhancer elements in the absence of TBX5, providing a potential mechanism for disrupted loop formation. These results highlight the importance of lineage-restricted TF dosage in cell type-specific 3D chromatin dynamics, suggesting a new mechanism for TF-dependent disease.
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Also filed as BioProject PRJNA1199549 and SRA study SRP552112. Searching any of these in the dataset finder brings you back here.

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