Transcription factor that plays an essential role in both trophoblast giant cell differentiation and in cardiac morphogenesis (PubMed:9500551, PubMed:16759287). Binds the DNA sequence 5'-NRTCTG-3' (non-canonical E-box) (PubMed:7791788). Acts as a transcriptional repressor of SOX15 (PubMed:16759287). In the adult, could be required for ongoing expression of cardiac-specific genes (By similarity). Efficient DNA binding requires dimerization with another bHLH protein. Forms homodimers and heterodimers with TCF3 gene products E12 and E47, HAND2 and HEY1, HEY2 and HEYL (hairy-related transcription factors). Interacts with MDFIC. Interacts with SOX15; the interaction enhances HAND1-induced differentiation of trophoblast giant cells (PubMed:16759287). Interaction with MDFIC sequesters it into the nucleolus, preventing the transcription factor activity. Phosphorylation by PLK4 disrupts the interaction with MDFIC and releases it from the nucleolus, leading to transcription factor activity. Smooth muscle cells of the gut and adrenal tissue. Present as a maternal transcript in the egg as well as during cleavage development before blastocyst formation. At 7.5 dpc, strongly expressed in all trophoblast cells (PubMed:16759287). Expression seen in the ectoplacental cone and extraembryonic mesodermal components of the amnion, allantois and visceral yolk sac. This high extraembryonic expression persists in the embryonic component of the placenta throughout development. In the embryo, expressed at 7.75 dpc in the lateral mesoderm along the entire length of the embryo as well as throughout the precardiogenic mesoderm. At 8.0 dpc, in the developing heart, expression becomes restricted to the rostral and caudal regions of the straight heart tube, which are fated to form the conotruncus and left ventricle, respectively. Symmetric expression is observed along the left-right axis in the caudal heart tube and lateral mesoderm. As cardiac looping occurs, the interrupted anterior-posterior patterning is maintained with expression in the future left, but not right ventricle. Expressed in the myocardium, but not in the endocardium, and specifically on the greater curvature of the looping heart which is opposed to the pericardium. After day 10.5 dpc, the high cardiac expression level declines abruptly. By 13.5 dpc, expression in the heart is restricted to the regions of valve formation. Besides the heart, expression becomes detectable in the gut at 9.0 dpc. At 10.0 dpc, expressed also in the lateral mesoderm and in the neural crest-derived branchial arches. At 10.5 dpc prominent expression in the gut, pharyngeal arches and in sympathetic ganglion primordia. At that stage, a low level of transient expression is seen in the distal posterior region of the limb bud. At 12 dpc expressed in the conceptus trophoblast giant cell layer in the placenta (PubMed:16759287). At 13.5 dpc expressed in neural crest derivatives, with abundant expression in the autonomic nervous system and adrenal medulla. Phosphorylation by PLK4 disrupts the interaction with MDFIC and leads to translocation into the nucleoplasm, allowing dimerization and transcription factor activity.