GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE307nnn/GSE307021/suppl/GSE307021_TBX5_degron_gene_fpkm.txt.gzftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE307nnn/GSE307021/suppl/GSE307021_TBX5_degron_gene_count.txt.gzftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE307nnn/GSE307021/primaryOK200TranscriptomicsHomo sapiensExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE307021GEOGSEfalseDose-dependent sensitivity of human 3D chromatin to a heart disease-linked transcription factor [RNA-Seq 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.2026/07/08GSE307021GSM9214379GSM9214380GSM9214376GSM9214375GSM9214378GSM921437734281307021Homo sapiens