Epigenetics and Progenitor Cell Program, Fox Chase Cancer Center, Philadelphia, PA 19111, United States.
Curr Opin Genet Dev. 2010 Oct;20(5):512-8. doi: 10.1016/j.gde.2010.06.001. Epub 2010 Jun 28.
Cell growth and differentiation during developmental processes require the activation of many inducible genes. However, eukaryotic chromatin, which consists of DNA and histones, becomes a natural barrier impeding access to the functional transcription machinery. To break through the chromatin barrier, eukaryotic organisms have evolved the strategy of using poly(ADP-ribose) polymerase 1 (PARP1) to modulate chromatin structure and initiate the steps leading to gene expression control. As a structural protein in chromatin, enzymatically silent PARP1 inhibits transcription by contributing to the condensation of chromatin, which creates a barrier against gene transcription. However, once activated by environmental stimuli and developmental signals, PARP1 can modify itself and other chromatin-associated proteins, thereby loosening chromatin to facilitate gene transcription. Here we discuss the roles of PARP1 in transcriptional control during development.
在发育过程中,细胞的生长和分化需要激活许多诱导基因。然而,真核染色质由 DNA 和组蛋白组成,它成为了阻碍功能转录机制的天然屏障。为了突破染色质屏障,真核生物进化出了一种利用多聚(ADP-核糖)聚合酶 1(PARP1)来调节染色质结构并启动基因表达控制步骤的策略。作为染色质中的结构蛋白,无酶活性的 PARP1 通过促进染色质的凝聚来抑制转录,从而形成阻止基因转录的屏障。然而,一旦被环境刺激和发育信号激活,PARP1 就可以修饰自身和其他与染色质相关的蛋白质,从而使染色质松动,促进基因转录。在这里,我们讨论了 PARP1 在发育过程中转录控制中的作用。