Groucho proteins: transcriptional corepressors for specific subsets of DNA-binding transcription factors in vertebrates and invertebrates (original) (raw)

  1. Alfred L. Fisher and
  2. Michael Caudy1
  3. Department of Cell Biology and Anatomy, Cornell University Medical College, New York, New York 10021 USA

Extensive analysis during the last 10–15 years has identified many of the mechanisms and factors involved in the activation of eukaryotic gene transcription. Although activation is better studied and more appreciated, a growing body of work has shown that in many circumstances transcriptional repression is as important as activation in the regulation of gene expression (Gray and Levine 1996). Studies of the development of the Drosophila peripheral nervous system (PNS) have revealed that a family of basic helix–loop–helix (bHLH) transcriptional repressors, known as the Hairy-related proteins, plays critical roles during development by repressing target genes at multiple stages of neurogenesis (Fisher and Caudy 1998). Similarly, the early patterning of the _Drosophila_embryo requires genes encoding transcriptional repressor proteins as well as transcriptional activator proteins, and mutations in either the activators or repressors result in lethal defects in patterning (Carroll 1990; Gray and Levine 1996). In mammals, the expression of certain neuron-specific genes like the type II sodium channel is restricted to neurons by the REST/NRSF protein that transcriptionally represses these genes in the non-neuronal cells in which REST/NRSF is expressed (Chong et al. 1995;Schoenherr and Anderson 1995). In humans, the DAX-1 gene, which is mutated in congenital X-linked adrenal hypoplasia, encodes a transcriptional repressor, and mutations responsible for the disease phenotype map to its repression domain (Lalli et al. 1997; Zazopoulos et al. 1997). This review focuses on a family of transcriptional corepressor proteins, known as Groucho proteins, that are found in flies, mice, humans, frogs, and worms.

Groucho, the founding member of this family, was identified initially as a mutation that affects the development of the _Drosophila_nervous system, with one allele resulting in thick tufts of sensory bristles over the eyes, resembling the bushy eyebrows of the comedian Groucho Marx. The Groucho proteins serve …