Regulating Gene Expression: The Design of Synthetic Transcriptional Regulators

Gene expression is a central phenomenon in all organisms. The first step in the expression of a gene is the transcription of the DNA to generate a messenger RNA, which is subsequently translated to a protein. In response to cellular and environmental cues regulatory proteins, known as transcriptional activators or repressors, either enhance or inhibit transcription of specific genes. Here, a summary of our current understanding of this initial step in gene expression is presented, along with the recent advances in creating synthetic analogs of regulatory transcription factors. The study of transcriptional regulation of an individual gene as well as that of all genes in the genome is now accessible to rational chemical intervention. The current challenges in the design of small-molecule transcription factors and their potential role in generating novel transcription-based therapeutics are also discussed.