Groucho/TLE family proteins and transcriptional repression

The Drosophila Groucho (Gro) protein is the prototype for a large family of corepressors, examples of which are found in most metazoans. This family i ncludes the human transducin-like Enhancer of split (TLE) proteins. As core pressors, Gro/TLE family proteins do not bind to DNA directly, but rather a re recruited to the template by DNA-bound repressor proteins. Gro/TLE famil y proteins are required for many developmental processes, including lateral inhibition, segmentation, sex determination, dorsal/ventral pattern format ion, terminal pattern formation, and eye development. These proteins are ch aracterized by a conserved N-terminal glutamine-rich domain and a conserved C-terminal WD-repeat domain. The primary role of the glutamine-rich domain is apparently to mediate tetramerization, while the WD-repeat domain may m ediate interactions with DNA-bound repressors. The glutamine rich and WD-re peat domains are separated by a less conserved region containing domains th at have been implicated in transcriptional repression and nuclear localizat ion. In addition to encoding full-length Gro/TLE family proteins, most meta zoan genomes encode truncated family members that contain the N-terminal ol igomerization domain, but lack the C-terminal WD-repeat domain. These trunc ated proteins may negatively regulate full-length Gro/TLE proteins, perhaps by sequestering them in nonproductive complexes. Gro/TLE family proteins p robably repress transcription by multiple mechanisms. For example, a glycin e/proline-rich domain in the central variable region functions to recruit t he histone deacetylase Rpd3 to the template. This histone deacetylase then presumably silences transcription by altering local chromatin structure. Ot her repression domains in Gro may function in a histone deacetylase-indepen dent manner. Many aspects of Gro/TLE protein function remain to be explored , including the possible post-translational regulation of Gro/TLE activity as well as the mechanisms by which Gro/TLE proteins direct repression at a distance. (C) 2000 Published by Elsevier Science B.V. All rights reserved.