EXPERIMENT_TITLE: Hi-C of Homo sapiens: ventricular cardiomyocyte differentiation from WTC11 at D11 rep1
STUDY_DESCRIPTOR_STUDY_ABSTRACT: Dosage-sensitive transcription factors (TFs) underlie altered gene regulation in congenital heart disease (CHD), and cell-type specific gene regulation is linked to the reorganization of 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. Regions normally bound by TBX5 were especially sensitive, while co-occupancy with CTCF partially protected TBX5-bound TAD boundaries and loop anchors. 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.
SAMPLE_SAMPLE_ATTRIBUTES_SAMPLE_ATTRIBUTE: [{"TAG": "isolate", "VALUE": "D11 of ventricular cardiomyocyte (CM) differentiation rep1"}, {"TAG": "age", "VALUE": "NA"}, {"TAG": "biomaterial_provider", "VALUE": "NA"}, {"TAG": "collection_date", "VALUE": "NA"}, {"TAG": "geo_loc_name", "VALUE": "NA"}, {"TAG": "sex", "VALUE": "not applicable"}, {"TAG": "tissue", "VALUE": "NA"}, {"TAG": "BioSampleModel", "VALUE": "Human"}]
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