A global view of genomic information--moving beyond the gene and the master regulator

The current view of gene regulation in complex organisms holds that gene expression is largely controlled by the combinatoric actions of transcription factors and other regulatory proteins, some of which powerfully influence cell type. Recent large-scale studies have confirmed that cellular differentiation involves many different regulatory factors. However, other studies indicate that the genome is pervasively transcribed to produce a variety of short and long non-protein-coding RNAs, including those derived from retrotransposed sequences, which also play important roles in the epigenetic regulation of gene expression. The evidence suggests that ontogenesis requires interplay between state-specific regulatory proteins, multitasked effector complexes and target-specific RNAs that recruit these complexes to their sites of action. Moreover, the semi-continuous nature of the transcriptome prompts the reassessment of 'genes' as discrete entities and indicates that the mammalian genome might be more accurately viewed as islands of protein-coding information in a sea of cis- and trans-acting regulatory sequences.