We are pleased to bring you Nature Milestones in Gene Expression – a supplement representing a collaborative effort between Nature Cell Biology and other Nature journals.

As in preceding Nature Milestones supplements, we chart landmark discoveries in a field with a series of short summaries of original papers. Here, we cover the key papers that reported groundbreaking findings in transcription, chromatin and epigenetics over the past 50 years, against the backdrop of established views at the time of their publication and their impact on the evolution of the field. The 23 Milestones and the discussed papers were selected with the assistance of a panel of 36 experts.

A swathe of processes including post-transcriptional, translational and even post-translational events can arguably fall under the remit of 'gene expression'. Covering these diverse aspects is beyond the scope of a single Milestones issue, and therefore we have focused on three aspects of gene expression that are inextricably linked — transcription, chromatin and epigenetic regulation.

These Milestones begin with studies in prokaryotes and bacteriophages that laid the foundations of the field by providing some of the earliest conceptual and experimental frameworks for studying transcription. Transcriptional regulation is undeniably more complex in higher eukaryotes, and this is illustrated in several milestones that discuss topics such as the identification of the different eukaryotic RNA polymerases; the discovery of the elaborate transcriptional activation machinery and its mechanism of action; and the discovery of enhancer elements to control transcription. Although the significance of chromatin in transcription was dismissed for many years, it is ironic that much of today's effort is focused on understanding the processes that unravel chromatin, and explaining how covalent modifications of histones and DNA control gene expression. Beginning with a discussion of the nucleosome hypothesis, we highlight the series of findings that ultimately led to a dramatic shift in the direction of the field towards understanding the impact of chromatin on gene expression. A distinct theme that emerges from these articles is that a combination of genetics, biochemistry and structural studies underpin progress in this area, and that often key developments have been driven by complementary findings in different model systems. We hope that the Milestones in Gene Expression will be equally enjoyable and informative for both the aficionado and the novice. This content is freely available on a dedicated web site (http://www.nature.com/milestones/geneexpression) until June 2006.

We acknowledge the financial support of Applied Biosystems, Agendia BV, the March of Dimes and the Juvenile Diabetes Research Foundation, which made it possible for the content to be freely available. As always, Nature Publishing Group carries sole responsibility for the editorial content.