Genome that makes the genetic information source for life and is the primary substrate for evolution, contains the genes that shape the forms and functions of life. Genome sequencing projects of large number of organisms, however, reveal that complexity in forms of life has evolved not by more number of genes, although more complex organisms do, in general, have bigger genomes compared to relatively simpler organisms. This additional DNA component likely brings in the regulatory features that eventually lead to evolution of complexity with similar number of genes. The important question that emerges from these observations is about the regulatory elements that generate greater number of cell types from identical genome in higher organisms, which is the key indicator of complexity. We have used bioinformatic and experimental approaches to analyse genomic sequences to identify and test potential regulatory elements in genomes using genetically amenable model systems. In addition to DNA elements, we have also analysed proteins that are epigenetic regulatory factors. Our analysis indicates an expansion of such epigenetic factors with the emergence of vertebrates. Taken together, it appears that cis regulatory elements and epigenetic factors together represent large proportion of regulatory content of the genome that has led to the evolution of complexity.