This chapter discusses the main ways in which gene expression is regulated, with a focus on those genes that encode proteins as their final product. Although some of these control mechanisms apply to both eukaryotes and prokaryotes, eukaryotic cells—with their more complex chromosomal structure—have some ways of controlling gene expression that are not available to bacteria. Gene expression is a complex process by which cells selectively direct the synthesis of the many thousands of proteins and RNAs encoded in their genome. Because eukaryotic transcription regulators can control transcription initiation when bound to DNA many base pairs away from the promoter, the nucleotide sequences that control the expression of a gene can be spread over long stretches of DNA. MicroRNAs control gene expression by base-pairing with specific mRNAs and inhibiting their stability and translation. In eukaryotes, the expression of a gene is generally controlled by a combination of different transcription regulator proteins.