GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE307nnn/GSE307018/ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE307nnn/GSE307018/suppl/GSE307018_TBX5_D20_DMSO_24h.mcoolftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE307nnn/GSE307018/suppl/GSE307018_TBX5_D20_dTAG_24h.mcoolprimaryOK200OtherHomo sapiensOtherhttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE307018GEOGSEfalseDose-dependent sensitivity of human 3D chromatin to a heart disease-linked transcription factor [Hi-C 2]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.2026/07/08GSE307018GSM9214343GSM9214342GSM9214345GSM921434434281307018Homo sapiens