Co-repressors 2000.
In the last 5 years, many co-repressors have been identified in eukaryotes that function in a wide range of species, from yeast to Drosophila and humans. Co-repressors are coregulators that are recruited by DNA-bound transcriptional silencers and play essential roles in many pathways including differentiation, proliferation, programmed cell death, and cell cycle. Accordingly, it has been shown that aberrant interactions of co-repressors with transcriptional silencers provide the molecular basis of a variety of human diseases. Co-repressors mediate transcriptional silencing by mechanisms that include direct inhibition of the basal transcription machinery and recruitment of chromatin-modifying enzymes. Chromatin modification includes histone deacetylation, which is thought to lead to a compact chromatin structure to which the accessibility of transcriptional activators is impaired. In a general mechanistic view, the overall picture suggests that transcriptional silencers and co-repressors act in analogy to transcriptional activators and coactivators, but with the opposite effect leading to gene silencing. We provide a comprehensive overview of the currently known higher eukaryotic co-repressors, their mechanism of action, and their involvement in biological and pathophysiological pathways. We also show the different pathways that lead to the regulation of co-repressor-silencer complex formation.
Burke
L J
LJ
Genetic Institute, Justus Liebig University, Heinrich Buff Ring 58-62, D-35392 Giessen, Germany.
Baniahmad
A
A
D002843:Chromatin / Q000378:metabolism; D020868:Gene Silencing; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D007938:Leukemia / Q000209:etiology; D008957:Models, Genetic; D011485:Protein Binding; D012097:Repressor Proteins / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*
D002843:Chromatin; D056572:Histone Deacetylase Inhibitors; D012097:Repressor Proteins; D014157:Transcription Factors