1% of babies are born with Congenital Heart Disease (CHD), manifesting as anatomical heart defects which often require treatment in the form of open-heart surgery within the first year of life. The causes of CHD have been attributed to environment and genetic factors but the aetiology of more than 80% of CHD cases remains unknown, making diagnosis and evaluation of the risk of the disease inheritance difficult. Our team has a long-standing interest in identifying the specific gene sets required for the formation of a healthy heart based on the principle that perturbations in these genes will impair normal development, resulting in cardiac defects. Thousands of genes are expressed in the heart at any given time point during development, but which of these genes are critical for heart formation and play a significant role in CHD? To answer this question, we performed a genome-wide investigation of the regulatory properties of genes that are known to be involved in heart development and disease by performing DamID-chip, ChIP-seq and RNA-seq in cardiac cells. Our bioinformatic investigations followed by in vivo functional validation led us to identify novel genes and regulatory elements essential for heart development and disease. Here we propose to present novel genetic components of the cardiac gene regulatory network, including novel cardiac transcription factors and heart-specific enhancers.