Burke L J, Baniahmad A
Genetic Institute, Justus Liebig University, Heinrich Buff Ring 58-62, D-35392 Giessen, Germany.
FASEB J. 2000 Oct;14(13):1876-88. doi: 10.1096/fj.99-0943rev.
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.
在过去五年中，真核生物中已鉴定出许多共抑制因子，它们在从酵母到果蝇和人类等广泛物种中发挥作用。共抑制因子是由与DNA结合的转录沉默子招募的共调节因子，在包括分化、增殖、程序性细胞死亡和细胞周期在内的许多途径中发挥重要作用。因此，已经表明共抑制因子与转录沉默子的异常相互作用为多种人类疾病提供了分子基础。共抑制因子通过包括直接抑制基础转录机制和招募染色质修饰酶在内的机制介导转录沉默。染色质修饰包括组蛋白去乙酰化，这被认为会导致染色质结构紧凑，转录激活因子难以接近。从一般的机制观点来看，总体情况表明转录沉默子和共抑制因子的作用类似于转录激活因子和共激活因子，但具有相反的效果，导致基因沉默。我们全面概述了目前已知的高等真核生物共抑制因子、它们的作用机制以及它们在生物学和病理生理途径中的参与情况。我们还展示了导致共抑制因子 - 沉默子复合物形成调节的不同途径。
