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 tran‐scriptional 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 si‐lencers and co‐repressors act in analogy to transcriptional activators and coactivators, but with the oppo‐site 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 dif‐ferent pathways that lead to the regulation of co‐repressor–silencer complex formation.—Burke, L. J., Baniahmad, A. Co‐repressors 2000. FASEB J. 14, 1876–1888 (2000)

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