To understand the whole, you must know the parts: unraveling the roles of protein–DNA interactions in genome regulation

Abstract

The regulation of gene transcription is fundamental to the existence of complex multicellular organisms such as humans. This process dictates which genes are expressed in which tissues, and controls how various cell types grow, differentiate, and respond to their environments. Although the deciphering of the human genome sequence has given us the “source code” for life, we still know far too little about the mechanisms that control which sets of genes are active in which tissues, and how their expression is regulated. It is clear, however, that much of this system depends upon the sequence-specific interactions of regulatory proteins with particular genetic loci. To be able to unravel the details of these interactions on a genome-wide basis, it is necessary to know what proteins are bound to the DNA where in the genome, and to be able to monitor how those proteins change over time and in response to external stimuli. Developing a new technology to provide this information constitutes a “Grand Challenge” for Analytical Chemistry. In this brief article we outline the nature of this challenge, and propose one strategy to address it.