Fig. 3: 3D chromatin remodeling induces new interaction between PITX2 and SAN specific regulatory region resulting to PITX2 expression remodeling.

a Hi-C subtraction map of hiPSC-CM WT and hiPSC-CM 15Kb−/− (red indicates gain of interaction and blue indicates loss of interaction). Dashed triangles delimit the fused TAD. Coding genes are represented in blue and non-coding genes in green. b Annotation of the 4q25 region with ATAC-seq from adult atrial and ventricular tissues from CARE database (hg38) and from hiPSC-derived pacemaker-like cardiomyocytes. Genome conservation across 100 vertebrates is presenting with phyloP score. Location of AF associated region in the genome is highlight with a green horizontal line and location of PLAYRR in purple horizontal line. The Blue line highlights the open region containing the CTCF binding sites and gray lines highlight regulatory regions newly interacting with PITX2 (R1 and R2). Annotation of the 4q25 region with, ATAC-seq from hiPSC-CM WT, CUT&RUN tracks from hiPSC-CM WT using H3K27ac, H3K4me3 and H3K4me1. Annotation of R1 and R2 regulatory regions with human and mouse binding sites for cardiac transcription factors (ISL1, GATA4, NKX2-5, MEIS1, TEAD and TBX5). Genome tracks were generated using UCSC Genome browser with the reference genome assembly hg19.