Many forkheads in the road to regulation

Abstract

The Keystone Symposium on Forkhead Transcription Factor Networks in Development, Signalling and Disease took place between 13 and 17 January 2008, at the Zermatt Resort and Spa in Midway, Utah, USA, and was organized by K. Zaret, K. Kaestner and S. Mango. ![][1] Subjects ranging from chromatin remodelling to ageing, from human disease to avian song, and from metabolism and the cell cycle to structural biology and differentiation were all covered at this keystone symposium, and illustrate the diversity of forkhead transcription factors and their regulatory functions. Forkhead transcription factors, or ‘FOX’ proteins, are unified as a family of more than 40 conserved proteins, each of which contains a DNA‐binding domain of approximately 110 amino acids dubbed the ‘forkhead box’. The members of the family are subdivided alphabetically and numerically into subfamilies based on evolutionary conservation (Kaestner et al , 2000). Forkhead factors have essential roles in regulatory networks that are involved in development, signalling, metabolism and human disease. Here, we summarize the new information presented at the meeting, to emphasize the breadth of biological areas in which forkhead factors have crucial regulatory roles. We apologize to the many colleagues whose exciting work we could not include owing to space limitations. The evolutionarily conserved forkhead box has been structurally characterized by both X‐ray crystallography and nuclear magnetic resonance (NMR) spectroscopy, and resembles a butterfly or ‘winged helix’ that is reminiscent of the globular chromatin‐binding domain of linker histones H1 and H5 (Clark et al , 1993; Weigelt et al , 2002). However, unlike linker histones, which compact the chromatin structure, binding by forkhead factors relieves chromatin compaction at target enhancer and/or promoter sites, allowing the entry of other transcriptional activators to induce target gene expression (Cirillo et al , 2002). Relatively little is known about the mechanisms that define how forkhead factors choose among … [1]: /embed/graphic-1.gif