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. Author manuscript; available in PMC: 2023 May 31.
Published in final edited form as: Circulation. 2022 Apr 11;145(22):1663–1683. doi: 10.1161/CIRCULATIONAHA.121.055781

Figure 7. Model Illustrating 3D Epigenome Organization in Human DCM and How HAND1 Rewires Enhancer/Promoter Connectome to Contribute to Transcriptome Reprogramming and DCM Pathogenesis.

Figure 7.

DCM-enriched enhancer/promoter connectome largely resides in pre-established, high-order chromatin architectures and pre-accessible chromatin sites bound by reactivated HAND1. Ectopic expression of HAND1 in human iPSC-derived cardiomyocytes (hiPSC-CM) and DCM hearts induces a distinct gain of enhancer/promoter connectivity and increases the expression of their associated genes implicated for DCM etiology, subsequently leading to abnormal cardiomyocyte electrophysiology/morphology, cardiac dilation and dysfunction. This illustrates a model whereby a single transcription factor rewires genome-wide enhancer/promoter connectome to drive DCM pathogenesis.