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

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE307021 | GEO | 2026/07/08

REPOSITORIES: GEO

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			Action	DRS
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	GSE307021_TBX5_degron_gene_count.txt.gz	Txt
	GSE307021_TBX5_degron_gene_fpkm.txt.gz	Txt

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