Functional insights into cardiac enhancer regions continue to be made by studying TF occupancy and chromatin states upon the perturbation of cardiac TFs or signaling pathways in multiple organisms (e.g., Gata4, gata5, Nkx2.5, Tbx5/tbx5, Tbx20, Hand2/hand2, Isl1, Foxf, Fgfr, Mek, and Ras) (He et al., 2014; Luna-Zurita et al., 2016; Boogerd et al., 2017; Jia et al., 2018; Pawlak et al., 2019; Racioppi et al., 2019), as well as in a human congenital heart disease (CHD) model (cardiomyocytes with a disease-associated missense mutation of GATA4) (Ang et al., 2016). Here, HAND2 is linked to coronary artery disorder.